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  • Sub-ångström cryo-EM structure of a prion protofibril reveals a polar clasp
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2018-01-15
    Marcus Gallagher-Jones, Calina Glynn, David R. Boyer, Michael W. Martynowycz, Evelyn Hernandez, Jennifer Miao, Chih-Te Zee, Irina V. Novikova, Lukasz Goldschmidt, Heather T. McFarlane, Gustavo F. Helguera, James E. Evans, Michael R. Sawaya, Duilio Cascio, David S. Eisenberg, Tamir Gonen, Jose A. Rodriguez

    The atomic structure of the infectious, protease-resistant, β-sheet-rich and fibrillar mammalian prion remains unknown. Through the cryo-EM method MicroED, we reveal the sub-ångström-resolution structure of a protofibril formed by a wild-type segment from the β2–α2 loop of the bank vole prion protein. The structure of this protofibril reveals a stabilizing network of hydrogen bonds that link polar zippers within a sheet, producing motifs we have named ‘polar clasps’.

    更新日期:2018-01-15
  • Cryo-EM structure of the exocyst complex
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2018-01-15
    Kunrong Mei, Yan Li, Shaoxiao Wang, Guangcan Shao, Jia Wang, Yuehe Ding, Guangzuo Luo, Peng Yue, Jun-Jie Liu, Xinquan Wang, Meng-Qiu Dong, Hong-Wei Wang, Wei Guo

    The exocyst is an evolutionarily conserved octameric protein complex that mediates the tethering of post-Golgi secretory vesicles to the plasma membrane during exocytosis and is implicated in many cellular processes such as cell polarization, cytokinesis, ciliogenesis and tumor invasion. Using cryo-EM and chemical cross-linking MS (CXMS), we solved the structure of the Saccharomyces cerevisiae exocyst complex at an average resolution of 4.4 Å. Our model revealed the architecture of the exocyst and led to the identification of the helical bundles that mediate the assembly of the complex at its core. Sequence analysis suggests that these regions are evolutionarily conserved across eukaryotic systems. Additional cell biological data suggest a mechanism for exocyst assembly that leads to vesicle tethering at the plasma membrane.

    更新日期:2018-01-15
  • Visualization and analysis of non-covalent contacts using the Protein Contacts Atlas
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2018-01-15
    Melis Kayikci, A. J. Venkatakrishnan, James Scott-Brown, Charles N. J. Ravarani, Tilman Flock, M. Madan Babu

    Visualizations of biomolecular structures empower us to gain insights into biological functions, generate testable hypotheses, and communicate biological concepts. Typical visualizations (such as ball and stick) primarily depict covalent bonds. In contrast, non-covalent contacts between atoms, which govern normal physiology, pathogenesis, and drug action, are seldom visualized. We present the Protein Contacts Atlas, an interactive resource of non-covalent contacts from over 100,000 PDB crystal structures. We developed multiple representations for visualization and analysis of non-covalent contacts at different scales of organization: atoms, residues, secondary structure, subunits, and entire complexes. The Protein Contacts Atlas enables researchers from different disciplines to investigate diverse questions in the framework of non-covalent contacts, including the interpretation of allostery, disease mutations and polymorphisms, by exploring individual subunits, interfaces, and protein–ligand contacts and by mapping external information. The Protein Contacts Atlas is available at http://www.mrc-lmb.cam.ac.uk/pca/ and also through PDBe.

    更新日期:2018-01-15
  • Structural biology of Zika virus and other flaviviruses
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2018-01-08
    S. Saif Hasan, Madhumati Sevvana, Richard J. Kuhn, Michael G. Rossmann

    Zika virus (ZIKV) is an enveloped, icosahedral flavivirus that has structural and functional similarities to other human flavivirus pathogens such as dengue (DENV), West Nile (WNV) and Japanese encephalitis (JEV) viruses. ZIKV infections have been linked to fetal microcephaly and the paralytic Guillain–Barré syndrome. This review provides a comparative structural analysis of the assembly, maturation and host-cell entry of ZIKV with other flaviviruses, especially DENV. We also discuss the mechanisms of neutralization by antibodies.

    更新日期:2018-01-09
  • Structure and dynamics of GPCR signaling complexes
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2018-01-08
    Daniel Hilger, Matthieu Masureel, Brian K. Kobilka

    G-protein-coupled receptors (GPCRs) relay numerous extracellular signals by triggering intracellular signaling through coupling with G proteins and arrestins. Recent breakthroughs in the structural determination of GPCRs and GPCR–transducer complexes represent important steps toward deciphering GPCR signal transduction at a molecular level. A full understanding of the molecular basis of GPCR-mediated signaling requires elucidation of the dynamics of receptors and their transducer complexes as well as their energy landscapes and conformational transition rates. Here, we summarize current insights into the structural plasticity of GPCR–G-protein and GPCR–arrestin complexes that underlies the regulation of the receptor’s intracellular signaling profile.

    更新日期:2018-01-09
  • Chd1 bends over backward to remodel
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2018-01-08
    Michaela M. Smolle

    Chd1 bends over backward to remodelChd1 bends over backward to remodel, Published online: 08 January 2018; doi:10.1038/s41594-017-0014-4Chd1 is a highly conserved chromatin remodeler found across all eukaryotic species. A recent study shows the structural changes that take place when yeast Chd1 binds to its nucleosomal substrate and reveals how they relate to remodeler function.

    更新日期:2018-01-09
  • NSMB at 25
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2018-01-08

    NSMB at 25 <i>NSMB</i> at 25, Published online: 08 January 2018; doi:10.1038/s41594-017-0017-1This January 2018 issue starts the 25th year of NSMB’s journey. We mark the occasion by launching a special series that celebrates the exciting research uncovering the fundamental principles behind biological processes.

    更新日期:2018-01-09
  • Spatiotemporal allele organization by allele-specific CRISPR live-cell imaging (SNP-CLING)
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2018-01-08
    Philipp G. Maass, A. Rasim Barutcu, David M. Shechner, Catherine L. Weiner, Marta Melé, John L. Rinn

    Imaging and chromatin capture techniques have provided important insights into our understanding of nuclear organization. A limitation of these techniques is the inability to resolve allele-specific spatiotemporal properties of genomic loci in living cells. Here, we describe an allele-specific CRISPR live-cell DNA imaging technique (SNP-CLING) to provide the first comprehensive insights into allelic positioning across space and time in mouse embryonic stem cells and fibroblasts. With 3D imaging, we studied alleles on different chromosomes in relation to one another and relative to nuclear substructures such as the nucleolus. We find that alleles maintain similar positions relative to each other and the nucleolus; however, loci occupy unique positions. To monitor spatiotemporal dynamics by SNP-CLING, we performed 4D imaging and determined that alleles are either stably positioned or fluctuating during cell state transitions, such as apoptosis. SNP-CLING is a universally applicable technique that enables the dissection of allele-specific spatiotemporal genome organization in live cells.

    更新日期:2018-01-08
  • MLL2 conveys transcription-independent H3K4 trimethylation in oocytes
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2018-01-01
    Courtney W. Hanna, Aaron Taudt, Jiahao Huang, Lenka Gahurova, Andrea Kranz, Simon Andrews, Wendy Dean, A. Francis Stewart, Maria Colomé-Tatché, Gavin Kelsey

    Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyte provides an attractive system to investigate these mechanisms, because extensive H3K4me3 acquisition occurs in nondividing cells. We developed low-input chromatin immunoprecipitation to interrogate H3K4me3, H3K27ac and H3K27me3 marks throughout oogenesis. In nongrowing oocytes, H3K4me3 was restricted to active promoters, but as oogenesis progressed, H3K4me3 accumulated in a transcription-independent manner and was targeted to intergenic regions, putative enhancers and silent H3K27me3-marked promoters. Ablation of the H3K4 methyltransferase gene Mll2 resulted in loss of transcription-independent H3K4 trimethylation but had limited effects on transcription-coupled H3K4 trimethylation or gene expression. Deletion of Dnmt3a and Dnmt3b showed that DNA methylation protects regions from acquiring H3K4me3. Our findings reveal two independent mechanisms of targeting H3K4me3 to genomic elements, with MLL2 recruited to unmethylated CpG-rich regions independently of transcription.

    更新日期:2018-01-01
  • Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2018-01-01
    Taylor E. T. Hughes, David T. Lodowski, Kevin W. Huynh, Aysenur Yazici, John Del Rosario, Abhijeet Kapoor, Sandip Basak, Amrita Samanta, Xu Han, Sudha Chakrapani, Z. Hong Zhou, Marta Filizola, Tibor Rohacs, Seungil Han, Vera Y. Moiseenkova-Bell

    The transient receptor potential vanilloid 5 (TRPV5) channel is a member of the transient receptor potential (TRP) channel family, which is highly selective for Ca2+, that is present primarily at the apical membrane of distal tubule epithelial cells in the kidney and plays a key role in Ca2+ reabsorption. Here we present the structure of the full-length rabbit TRPV5 channel as determined using cryo-EM in complex with its inhibitor econazole. This structure reveals that econazole resides in a hydrophobic pocket analogous to that occupied by phosphatidylinositides and vanilloids in TRPV1, thus suggesting conserved mechanisms for ligand recognition and lipid binding among TRPV channels. The econazole-bound TRPV5 structure adopts a closed conformation with a distinct lower gate that occludes Ca2+ permeation through the channel. Structural comparisons between TRPV5 and other TRPV channels, complemented with molecular dynamics (MD) simulations of the econazole-bound TRPV5 structure, allowed us to gain mechanistic insight into TRPV5 channel inhibition by small molecules.

    更新日期:2018-01-01
  • Bap (Sil1) regulates the molecular chaperone BiP by coupling release of nucleotide and substrate
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2018-01-01
    Mathias Rosam, Daniela Krader, Christina Nickels, Janine Hochmair, Katrin C. Back, Ganesh Agam, Anders Barth, Cathleen Zeymer, Jelle Hendrix, Markus Schneider, Iris Antes, Jochen Reinstein, Don C. Lamb, Johannes Buchner

    BiP is the endoplasmic member of the Hsp70 family. BiP is regulated by several co-chaperones including the nucleotide-exchange factor (NEF) Bap (Sil1 in yeast). Bap is a two-domain protein. The interaction of the Bap C-terminal domain with the BiP ATPase domain is sufficient for its weak NEF activity. However, stimulation of the BiP ATPase activity requires full-length Bap, suggesting a complex interplay of these two factors. Here, single-molecule FRET experiments with mammalian proteins reveal that Bap affects the conformation of both BiP domains, including the lid subdomain, which is important for substrate binding. The largely unstructured Bap N-terminal domain promotes the substrate release from BiP. Thus, Bap is a conformational regulator affecting both nucleotide and substrate interactions. The preferential interaction with BiP in its ADP state places Bap at a late stage of the chaperone cycle, in which it coordinates release of substrate and ADP, thereby resetting BiP for ATP and substrate binding.

    更新日期:2018-01-01
  • Nucleotide exchange factors Fes1 and HspBP1 mimic substrate to release misfolded proteins from Hsp70
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2018-01-01
    Naveen K. C. Gowda, Jayasankar M. Kaimal, Roman Kityk, Chammiran Daniel, Jobst Liebau, Marie Öhman, Matthias P. Mayer, Claes Andréasson

    Protein quality control depends on the tight regulation of interactions between molecular chaperones and polypeptide substrates. Substrate release from the chaperone Hsp70 is triggered by nucleotide-exchange factors (NEFs) that control folding and degradation fates via poorly understood mechanisms. We found that the armadillo-type NEFs budding yeast Fes1 and its human homolog HspBP1 employ flexible N-terminal release domains (RDs) with substrate-mimicking properties to ensure the efficient release of persistent substrates from Hsp70. The RD contacts the substrate-binding domain of the chaperone, competes with peptide substrate for binding and is essential for proper function in yeast and mammalian cells. Thus, the armadillo domain engages Hsp70 to trigger nucleotide exchange, whereas the RD safeguards the release of substrates. Our findings provide fundamental mechanistic insight into the functional specialization of Hsp70 NEFs and have implications for the understanding of proteostasis-related disorders, including Marinesco–Sjögren syndrome.

    更新日期:2018-01-01
  • RNA-DamID reveals cell-type-specific binding of roX RNAs at chromatin-entry sites
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-12-18
    Seth W. Cheetham, Andrea H. Brand

    Thousands of long noncoding RNAs (lncRNAs) have been identified in eukaryotic genomes, many of which are expressed in spatially and temporally restricted patterns. Nonetheless, the roles of the majority of these transcripts are still unknown. One of the mechanisms by which lncRNAs function is through the modulation of chromatin states. To assess the functions of lncRNAs, we developed RNA-DamID, a novel approach that detects lncRNA–genome interactions in a cell-type-specific manner in vivo with high sensitivity and accuracy. Identifying the cell-type-specific genome occupancy of lncRNAs is vital to understanding their mechanisms of action in development and disease. We used RNA-DamID to investigate targeting of the lncRNAs in the Drosophila dosage-compensation complex (DCC) and show that initial targeting is cell-type specific.

    更新日期:2017-12-18
  • APOBEC3 induces mutations during repair of CRISPR–Cas9-generated DNA breaks
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-12-11
    Liqun Lei, Hongquan Chen, Wei Xue, Bei Yang, Bian Hu, Jia Wei, Lijie Wang, Yiqiang Cui, Wei Li, Jianying Wang, Lei Yan, Wanjing Shang, Jimin Gao, Jiahao Sha, Min Zhuang, Xingxu Huang, Bin Shen, Li Yang, Jia Chen

    The APOBEC-AID family of cytidine deaminase prefers single-stranded nucleic acids for cytidine-to-uridine deamination. Single-stranded nucleic acids are commonly involved in the DNA repair system for breaks generated by CRISPR–Cas9. Here, we show in human cells that APOBEC3 can trigger cytidine deamination of single-stranded oligodeoxynucleotides, which ultimately results in base substitution mutations in genomic DNA through homology-directed repair (HDR) of Cas9-generated double-strand breaks. In addition, the APOBEC3-catalyzed deamination in genomic single-stranded DNA formed during the repair of Cas9 nickase-generated single-strand breaks in human cells can be further processed to yield mutations mainly involving insertions or deletions (indels). Both APOBEC3-mediated deamination and DNA-repair proteins play important roles in the generation of these indels. Therefore, optimizing conditions for the repair of CRISPR–Cas9-generated DNA breaks, such as using double-stranded donors in HDR or temporarily suppressing endogenous APOBEC3s, can repress these unwanted mutations in genomic DNA.

    更新日期:2017-12-11
  • Dominant-negative SMARCA4 mutants alter the accessibility landscape of tissue-unrestricted enhancers
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-12-11
    H. Courtney Hodges, Benjamin Z. Stanton, Katerina Cermakova, Chiung-Ying Chang, Erik L. Miller, Jacob G. Kirkland, Wai Lim Ku, Vaclav Veverka, Keji Zhao, Gerald R. Crabtree

    Mutation of SMARCA4 (BRG1), the ATPase of BAF (mSWI/SNF) and PBAF complexes, contributes to a range of malignancies and neurologic disorders. Unfortunately, the effects of SMARCA4 missense mutations have remained uncertain. Here we show that SMARCA4 cancer missense mutations target conserved ATPase surfaces and disrupt the mechanochemical cycle of remodeling. We find that heterozygous expression of mutants alters the open chromatin landscape at thousands of sites across the genome. Loss of DNA accessibility does not directly overlap with Polycomb accumulation, but is enriched in ‘A compartments’ at active enhancers, which lose H3K27ac but not H3K4me1. Affected positions include hundreds of sites identified as superenhancers in many tissues. Dominant-negative mutation induces pro-oncogenic expression changes, including increased expression of Myc and its target genes. Together, our data suggest that disruption of enhancer accessibility represents a key source of altered function in disorders with SMARCA4 mutations in a wide variety of tissues.

    更新日期:2017-12-11
  • Histone octamer rearranges to adapt to DNA unwrapping
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-12-11
    Silvija Bilokapic, Mike Strauss, Mario Halic

    Nucleosomes, the basic units of chromatin, package and regulate expression of eukaryotic genomes. Although the structure of the intact nucleosome is well characterized, little is known about structures of partially unwrapped, transient intermediates. In this study, we present nine cryo-EM structures of distinct conformations of nucleosome and subnucleosome particles. These structures show that initial DNA breathing induces conformational changes in the histone octamer, particularly in histone H3, that propagate through the nucleosome and prevent symmetrical DNA opening. Rearrangements in the H2A–H2B dimer strengthen interaction with the unwrapping DNA and promote nucleosome stability. In agreement with this, cross-linked H2A–H2B that cannot accommodate unwrapping of the DNA is not stably maintained in the nucleosome. H2A–H2B release and DNA unwrapping occur simultaneously, indicating that DNA is essential in stabilizing the dimer in the nucleosome. Our structures reveal intrinsic nucleosomal plasticity that is required for nucleosome stability and might be exploited by extrinsic protein factors.

    更新日期:2017-12-11
  • Polθ helicase: drive or reverse
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-12-07
    Judith L Campbell, Hongzhi Li

    Polθ helicase: drive or reverse Polθ helicase: drive or reverse, Published online: 07 December 2017; doi:10.1038/nsmb.3510 The helicase intrinsic to DNA polymerase θ (Polθ), the versatile mediator of microhomology-based repair of DNA double-strand breaks and stalled replication forks, is now revealed to be a member of an elite group of proteins known as annealing helicases. This small family of enzymes remodels DNA intermediates in multiple repair processes that are crucial to preserving genome stability and warding off cancer and aging.

    更新日期:2017-12-07
  • One flexible loop in OST lassos both substrates
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-12-07
    Shiteshu Shrimal, Natalia A Cherepanova, Reid Gilmore

    One flexible loop in OST lassos both substrates One flexible loop in OST lassos both substrates, Published online: 07 December 2017; doi:10.1038/nsmb.3508 The crystal structure of an oligosaccharyltransferase in complex with a sugar donor and an acceptor peptide provides insight into the mechanism of protein glycosylation and reveals how lipid-linked oligosaccharides are positioned in the enzyme active site.

    更新日期:2017-12-07
  • The ribosome moves: RNA mechanics and translocation
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-12-07
    Harry F Noller, Laura Lancaster, Jie Zhou, Srividya Mohan

    The ribosome moves: RNA mechanics and translocation The ribosome moves: RNA mechanics and translocation, Published online: 07 December 2017; doi:10.1038/nsmb.3505 The mechanics and mechanisms of ribosomal translocation, including the conformational rearrangements in the ribosome and the roles of EF-G and tRNAs, are discussed in this Perspective by Mohan, Noller and colleagues.

    更新日期:2017-12-07
  • Catching DNA with hoops—biophysical approaches to clarify the mechanism of SMC proteins
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-12-07
    Jorine Eeftens, Cees Dekker

    Catching DNA with hoops—biophysical approaches to clarify the mechanism of SMC proteins Catching DNA with hoops—biophysical approaches to clarify the mechanism of SMC proteins, Published online: 07 December 2017; doi:10.1038/nsmb.3507 In this Review, the authors consider how single-molecule biophysical approaches can inform our understanding of the ring-shaped structural maintenance of chromosome (SMC) complexes and their function in chromosome organization.

    更新日期:2017-12-07
  • Poly(A) tails: longer is not always better
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-12-07
    Luciana A Castellano, Ariel A Bazzini

    Poly(A) tails: longer is not always better Poly(A) tails: longer is not always better, Published online: 07 December 2017; doi:10.1038/nsmb.3509 Deadenylation of mRNAs is generally associated with translational inhibition and mRNA decay. A study now reports that, unexpectedly, highly expressed genes tend to have shorter poly(A) tails and suggests that poly(A) tails can be 'pruned', generating a 30-nucleotide-biased phased distribution, likely due to protection by poly(A)-binding proteins.

    更新日期:2017-12-07
  • Cryo-EM structures of the human INO80 chromatin-remodeling complex
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-12-04
    Ricardo J. Aramayo, Oliver Willhoft, Rafael Ayala, Rohan Bythell-Douglas, Dale B. Wigley, Xiaodong Zhang

    Access to chromatin for processes such as transcription and DNA repair requires the sliding of nucleosomes along DNA. This process is aided by chromatin-remodeling complexes, such as the multisubunit INO80 chromatin-remodeling complex. Here we present cryo-EM structures of the active core complex of human INO80 at 9.6 Å, with portions at 4.1-Å resolution, and reconstructions of combinations of subunits. Together, these structures reveal the architecture of the INO80 complex, including Ino80 and actin-related proteins, which is assembled around a single RUVBL1 (Tip49a) and RUVBL2 (Tip49b) AAA+ heterohexamer. An unusual spoked-wheel structural domain of the Ino80 subunit is engulfed by this heterohexamer; both, in combination, form the core of the complex. We also identify a cleft in RUVBL1 and RUVBL2, which forms a major interaction site for partner proteins and probably communicates these interactions to its nucleotide-binding sites.

    更新日期:2017-12-05
  • Two three-strand intermediates are processed during Rad51-driven DNA strand exchange
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-12-04
    Kentaro Ito, Yasuto Murayama, Masayuki Takahashi, Hiroshi Iwasaki

    During homologous recombination, Rad51 forms a nucleoprotein filament with single-stranded DNA (ssDNA) that undergoes strand exchange with homologous double-stranded DNA (dsDNA). Here, we use real-time analysis to show that strand exchange by fission yeast Rad51 proceeds via two distinct three-strand intermediates, C1 and C2. Both intermediates contain Rad51, but whereas the donor duplex remains intact in C1, the ssDNA strand is intertwined with the complementary strand of the donor duplex in C2. Swi5–Sfr1, an evolutionarily conserved recombination activator, facilitates the C1–C2 transition and subsequent ssDNA release from C2 to complete strand exchange in an ATP-hydrolysis-dependent manner. In contrast, Ca2+, which activates the Rad51 filament by curbing ATP hydrolysis, facilitates the C1–C2 transition but does not promote strand exchange. These results reveal that Swi5–Sfr1 and Ca2+ have different activation modes in the late synaptic phase, despite their common function in stabilizing the presynaptic filament.

    更新日期:2017-12-05
  • Postmitotic nuclear pore assembly proceeds by radial dilation of small membrane openings
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-27
    Shotaro Otsuka, Anna M. Steyer, Martin Schorb, Jean-Karim Hériché, M. Julius Hossain, Suruchi Sethi, Moritz Kueblbeck, Yannick Schwab, Martin Beck, Jan Ellenberg

    The nuclear envelope has to be reformed after mitosis to create viable daughter cells with closed nuclei. How membrane sealing of DNA and assembly of nuclear pore complexes (NPCs) are achieved and coordinated is poorly understood. Here, we reconstructed nuclear membrane topology and the structures of assembling NPCs in a correlative 3D EM time course of dividing human cells. Our quantitative ultrastructural analysis shows that nuclear membranes form from highly fenestrated ER sheets whose holes progressively shrink. NPC precursors are found in small membrane holes and dilate radially during assembly of the inner ring complex, forming thousands of transport channels within minutes. This mechanism is fundamentally different from that of interphase NPC assembly and explains how mitotic cells can rapidly establish a closed nuclear compartment while making it transport competent.

    更新日期:2017-11-28
  • Postmitotic nuclear pore assembly proceeds by radial dilation of small membrane openings
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-27
    Shotaro Otsuka, Anna M. Steyer, Martin Schorb, Jean-Karim Hériché, M. Julius Hossain, Suruchi Sethi, Moritz Kueblbeck, Yannick Schwab, Martin Beck, Jan Ellenberg

    The nuclear envelope has to be reformed after mitosis to create viable daughter cells with closed nuclei. How membrane sealing of DNA and assembly of nuclear pore complexes (NPCs) are achieved and coordinated is poorly understood. Here, we reconstructed nuclear membrane topology and the structures of assembling NPCs in a correlative 3D EM time course of dividing human cells. Our quantitative ultrastructural analysis shows that nuclear membranes form from highly fenestrated ER sheets whose holes progressively shrink. NPC precursors are found in small membrane holes and dilate radially during assembly of the inner ring complex, forming thousands of transport channels within minutes. This mechanism is fundamentally different from that of interphase NPC assembly and explains how mitotic cells can rapidly establish a closed nuclear compartment while making it transport competent.

    更新日期:2017-11-28
  • A consensus model of human apolipoprotein A-I in its monomeric and lipid-free state
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-13
    John T Melchior, Ryan G Walker, Allison L Cooke, Jamie Morris, Mark Castleberry, Thomas B Thompson, Martin K Jones, Hyun D Song, Kerry-Anne Rye, Michael N Oda, Mary G Sorci-Thomas, Michael J Thomas, Jay W Heinecke, Xiaohu Mei, David Atkinson, Jere P Segrest, Sissel Lund-Katz, Michael C Phillips, W Sean Davidson

    A consensus model of human apolipoprotein A-I in its monomeric and lipid-free state A consensus model of human apolipoprotein A-I in its monomeric and lipid-free state, Published online: 13 November 2017; doi:10.1038/nsmb.3501 NatureArticleSnippet(type=short-summary, markup= Apolipoprotein A-I (apoA-I) is the scaffold protein that is essential for the assembly and function of HDL particles. A structural model for monomeric, lipid-free apoA-I, based on previous and new data, is now presented. , isJats=true)

    更新日期:2017-11-13
  • Programming asynchronous replication in stem cells
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-13
    Hagit Masika, Marganit Farago, Merav Hecht, Reba Condiotti, Kirill Makedonski, Yosef Buganim, Tal Burstyn-Cohen, Yehudit Bergman, Howard Cedar

    Programming asynchronous replication in stem cells Programming asynchronous replication in stem cells, Published online: 13 November 2017; doi:10.1038/nsmb.3503 NatureArticleSnippet(type=short-summary, markup= Asynchronous replication-timing patterns undergo programmed switching between maternal and paternal alleles in embryonic and adult stem cells. , isJats=true)

    更新日期:2017-11-13
  • A consensus model of human apolipoprotein A-I in its monomeric and lipid-free state
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-13
    John T Melchior, Ryan G Walker, Allison L Cooke, Jamie Morris, Mark Castleberry, Thomas B Thompson, Martin K Jones, Hyun D Song, Kerry-Anne Rye, Michael N Oda, Mary G Sorci-Thomas, Michael J Thomas, Jay W Heinecke, Xiaohu Mei, David Atkinson, Jere P Segrest, Sissel Lund-Katz, Michael C Phillips, W Sean Davidson

    A consensus model of human apolipoprotein A-I in its monomeric and lipid-free state A consensus model of human apolipoprotein A-I in its monomeric and lipid-free state, Published online: 13 November 2017; doi:10.1038/nsmb.3501 NatureArticleSnippet(type=short-summary, markup= Apolipoprotein A-I (apoA-I) is the scaffold protein that is essential for the assembly and function of HDL particles. A structural model for monomeric, lipid-free apoA-I, based on previous and new data, is now presented. , isJats=true)

    更新日期:2017-11-13
  • Programming asynchronous replication in stem cells
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-13
    Hagit Masika, Marganit Farago, Merav Hecht, Reba Condiotti, Kirill Makedonski, Yosef Buganim, Tal Burstyn-Cohen, Yehudit Bergman, Howard Cedar

    Programming asynchronous replication in stem cells Programming asynchronous replication in stem cells, Published online: 13 November 2017; doi:10.1038/nsmb.3503 NatureArticleSnippet(type=short-summary, markup= Asynchronous replication-timing patterns undergo programmed switching between maternal and paternal alleles in embryonic and adult stem cells. , isJats=true)

    更新日期:2017-11-13
  • Ribosome origami
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-07
    Joanna Rorbach, Shintaro Aibara, Alexey Amunts

    Assembly of the small ribosomal subunit from an RNA strand and 33 proteins is an intricate and dynamic process. Two cryo-EM studies now provide insight into a complicated complex of at least 51 trans-factors that act on the preribosomal small subunit to sequentially fold it into a 3D molecular machine.

    更新日期:2017-11-08
  • Ribosome origami
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-01
    Joanna Rorbach, Shintaro Aibara, Alexey Amunts

    Assembly of the small ribosomal subunit from an RNA strand and 33 proteins is an intricate and dynamic process. Two cryo-EM studies now provide insight into a complicated complex of at least 51 trans-factors that act on the preribosomal small subunit to sequentially fold it into a 3D molecular machine.

    更新日期:2017-11-08
  • Extrachromosomal telomere repeat DNA is linked to ALT development via cGAS-STING DNA sensing pathway
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-06
    Yi-An Chen, Yi-Ling Shen, Hsuan-Yu Hsia, Yee-Peng Tiang, Tzu-Ling Sung, Liuh-Yow Chen

    Extrachromosomal telomere repeat (ECTR) DNA is unique to cancer cells that maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, but the role of ECTRs in ALT development remains elusive. We found that induction of ECTRs in normal human fibroblasts activated the cGAS-STING-TBK1-IRF3 signaling axis to trigger IFNβ production and a type I interferon response, resulting in cell-proliferation defects. In contrast, ALT cancer cells are commonly defective in sensing cytosolic DNA. We found that STING expression was inhibited in ALT cancer cell lines and transformed ALT cells. Notably, the ALT suppressors histone H3.3 and the ATRX–Daxx histone chaperone complex were also required to activate the DNA-sensing pathway. Collectively, our data suggest that the loss of the cGAS-STING pathway may be required to evade ECTR-induced anti-proliferation effects and permit ALT development, and this requirement may be exploited for treatments specific to cancers utilizing the ALT pathway.

    更新日期:2017-11-06
  • TFIIH generates a six-base-pair open complex during RNAP II transcription initiation and start-site scanning
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-06
    Eric J Tomko, James Fishburn, Steven Hahn, Eric A Galburt

    Eukaryotic mRNA transcription initiation is directed by the formation of the megadalton-sized preinitiation complex (PIC). After PIC formation, double-stranded DNA (dsDNA) is unwound to form a single-stranded DNA bubble, and the template strand is loaded into the polymerase active site. DNA opening is catalyzed by Ssl2 (XPB), the dsDNA translocase subunit of the basal transcription factor TFIIH. In yeast, transcription initiation proceeds through a scanning phase during which downstream DNA is searched for optimal start sites. Here, to test models for initial DNA opening and start-site scanning, we measure the DNA-bubble sizes generated by Saccharomyces cerevisiae PICs in real time using single-molecule magnetic tweezers. We show that ATP hydrolysis by Ssl2 opens a 6-base-pair (bp) bubble that grows to 13 bp in the presence of NTPs. These observations support a two-step model wherein ATP-dependent Ssl2 translocation leads to a 6-bp open complex that RNA polymerase II expands via NTP-dependent RNA transcription.

    更新日期:2017-11-06
  • Short poly(A) tails are a conserved feature of highly expressed genes
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-06
    Sarah Azoubel Lima, Laura B Chipman, Angela L Nicholson, Ying-Hsin Chen, Brian A Yee, Gene W Yeo, Jeff Coller, Amy E Pasquinelli

    Poly(A) tails are important elements in mRNA translation and stability, although recent genome-wide studies have concluded that poly(A) tail length is generally not associated with translational efficiency in nonembryonic cells. To investigate whether poly(A) tail size might be coupled to gene expression in an intact organism, we used an adapted TAIL-seq protocol to measure poly(A) tails in Caenorhabditis elegans. Surprisingly, we found that well-expressed transcripts contain relatively short, well-defined tails. This attribute appears to be dependent on translational efficiency, as transcripts enriched for optimal codons and ribosome association had the shortest tail sizes, whereas noncoding RNAs retained long tails. Across eukaryotes, short tails were a feature of abundant and well-translated mRNAs. This seems to contradict the dogma that deadenylation induces translational inhibition and mRNA decay and suggests that well-expressed mRNAs accumulate with pruned tails that accommodate a minimal number of poly(A)-binding proteins, which may be ideal for protective and translational functions.

    更新日期:2017-11-06
  • Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-06
    Xiaoyuan Zhou, Minghui Li, Deyuan Su, Qi Jia, Huan Li, Xueming Li, Jian Yang

    TRPML3 channels are mainly localized to endolysosomes and play a critical role in the endocytic pathway. Their dysfunction causes deafness and pigmentation defects in mice. TRPML3 activity is inhibited by low endolysosomal pH. Here we present cryo-electron microscopy (cryo-EM) structures of human TRPML3 in the closed, agonist-activated, and low-pH-inhibited states, with resolutions of 4.06, 3.62, and 4.65 Å, respectively. The agonist ML-SA1 lodges between S5 and S6 and opens an S6 gate. A polycystin-mucolipin domain (PMD) forms a luminal cap. S1 extends into this cap, forming a 'gating rod' that connects directly to a luminal pore loop, which undergoes dramatic conformational changes in response to low pH. S2 extends intracellularly and interacts with several intracellular regions to form a 'gating knob'. These unique structural features, combined with the results of electrophysiological studies, indicate a new mechanism by which luminal pH and other physiological modulators such as PIP2 regulate TRPML3 by changing S1 and S2 conformations.

    更新日期:2017-11-06
  • Extrachromosomal telomere repeat DNA is linked to ALT development via cGAS-STING DNA sensing pathway
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-06
    Yi-An Chen, Yi-Ling Shen, Hsuan-Yu Hsia, Yee-Peng Tiang, Tzu-Ling Sung, Liuh-Yow Chen

    Extrachromosomal telomere repeat (ECTR) DNA is unique to cancer cells that maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, but the role of ECTRs in ALT development remains elusive. We found that induction of ECTRs in normal human fibroblasts activated the cGAS-STING-TBK1-IRF3 signaling axis to trigger IFNβ production and a type I interferon response, resulting in cell-proliferation defects. In contrast, ALT cancer cells are commonly defective in sensing cytosolic DNA. We found that STING expression was inhibited in ALT cancer cell lines and transformed ALT cells. Notably, the ALT suppressors histone H3.3 and the ATRX–Daxx histone chaperone complex were also required to activate the DNA-sensing pathway. Collectively, our data suggest that the loss of the cGAS-STING pathway may be required to evade ECTR-induced anti-proliferation effects and permit ALT development, and this requirement may be exploited for treatments specific to cancers utilizing the ALT pathway.

    更新日期:2017-11-06
  • TFIIH generates a six-base-pair open complex during RNAP II transcription initiation and start-site scanning
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-06
    Eric J Tomko, James Fishburn, Steven Hahn, Eric A Galburt

    Eukaryotic mRNA transcription initiation is directed by the formation of the megadalton-sized preinitiation complex (PIC). After PIC formation, double-stranded DNA (dsDNA) is unwound to form a single-stranded DNA bubble, and the template strand is loaded into the polymerase active site. DNA opening is catalyzed by Ssl2 (XPB), the dsDNA translocase subunit of the basal transcription factor TFIIH. In yeast, transcription initiation proceeds through a scanning phase during which downstream DNA is searched for optimal start sites. Here, to test models for initial DNA opening and start-site scanning, we measure the DNA-bubble sizes generated by Saccharomyces cerevisiae PICs in real time using single-molecule magnetic tweezers. We show that ATP hydrolysis by Ssl2 opens a 6-base-pair (bp) bubble that grows to 13 bp in the presence of NTPs. These observations support a two-step model wherein ATP-dependent Ssl2 translocation leads to a 6-bp open complex that RNA polymerase II expands via NTP-dependent RNA transcription.

    更新日期:2017-11-06
  • Short poly(A) tails are a conserved feature of highly expressed genes
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-06
    Sarah Azoubel Lima, Laura B Chipman, Angela L Nicholson, Ying-Hsin Chen, Brian A Yee, Gene W Yeo, Jeff Coller, Amy E Pasquinelli

    Poly(A) tails are important elements in mRNA translation and stability, although recent genome-wide studies have concluded that poly(A) tail length is generally not associated with translational efficiency in nonembryonic cells. To investigate whether poly(A) tail size might be coupled to gene expression in an intact organism, we used an adapted TAIL-seq protocol to measure poly(A) tails in Caenorhabditis elegans. Surprisingly, we found that well-expressed transcripts contain relatively short, well-defined tails. This attribute appears to be dependent on translational efficiency, as transcripts enriched for optimal codons and ribosome association had the shortest tail sizes, whereas noncoding RNAs retained long tails. Across eukaryotes, short tails were a feature of abundant and well-translated mRNAs. This seems to contradict the dogma that deadenylation induces translational inhibition and mRNA decay and suggests that well-expressed mRNAs accumulate with pruned tails that accommodate a minimal number of poly(A)-binding proteins, which may be ideal for protective and translational functions.

    更新日期:2017-11-06
  • Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-11-06
    Xiaoyuan Zhou, Minghui Li, Deyuan Su, Qi Jia, Huan Li, Xueming Li, Jian Yang

    Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states, Published online: 06 November 2017; doi:10.1038/nsmb.3502 NatureArticleSnippet(type=short-summary, markup= Cryo-EM analyses of human TRPML3 reveal this channel in three different states—closed, agonist-activated and low-pH-inhibited—and suggest mechanisms for regulation. , isJats=true)

    更新日期:2017-11-06
  • Telomeric TERB1–TRF1 interaction is crucial for male meiosis
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-30
    Juanjuan Long, Chenhui Huang, Yanyan Chen, Ying Zhang, Shaohua Shi, Ligang Wu, Yie Liu, Chengyu Liu, Jian Wu, Ming Lei

    Telomeric TERB1–TRF1 interaction is crucial for male meiosis Nature Structural & Molecular Biology, Published online: 30 October 2017; doi:10.1038/nsmb.3496 Disrupting the interaction between telomere protein TRF1 with meiosis-specific protein TERB1 impairs the pairing of X and Y chromosomes via their telomere-adjacent pseudoautosomal regions in pachytene, leading to spermatocyte apoptosis and male infertility in mice.

    更新日期:2017-10-30
  • Dissecting the telomere–inner nuclear membrane interface formed in meiosis
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-30
    Devon F Pendlebury, Yasuhiro Fujiwara, Valerie M Tesmer, Eric M Smith, Hiroki Shibuya, Yoshinori Watanabe, Jayakrishnan Nandakumar

    Dissecting the telomere–inner nuclear membrane interface formed in meiosis Nature Structural & Molecular Biology, Published online: 30 October 2017; doi:10.1038/nsmb.3493 Structural and functional analyses of human TRF1 in complex with meiosis-specific protein TERB1 reveal the basis for telomere tethering to the inner nuclear membrane and offer insight into the mechanism of dissociation in late pachytene.

    更新日期:2017-10-30
  • Preribosomes escaping from the nucleus are caught during translation by cytoplasmic quality control
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-30
    Anshuk Sarkar, Matthias Thoms, Clara Barrio-Garcia, Emma Thomson, Dirk Flemming, Roland Beckmann, Ed Hurt

    Preribosomes escaping from the nucleus are caught during translation by cytoplasmic quality control Nature Structural & Molecular Biology, Published online: 30 October 2017; doi:10.1038/nsmb.3495 Abnormal pre-60S particles are able to escape nuclear quality control and join mature 40S subunits to catalyze cytoplasmic protein synthesis, but the resulting translation defects trigger the cytoplasmic surveillance machineries RQC and the Ski-exosome.

    更新日期:2017-10-30
  • Encoding optical control in LCK kinase to quantitatively investigate its activity in live cells
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-30
    Ardiyanto Liaunardy-Jopeace, Ben L Murton, Mohan Mahesh, Jason W Chin, John R James

    Encoding optical control in LCK kinase to quantitatively investigate its activity in live cells Nature Structural & Molecular Biology, Published online: 30 October 2017; doi:10.1038/nsmb.3492 Engineering an LCK mutant, in which an active-site lysine is replaced by a photocaged equivalent via genetic code expansion, allows quantitation of phosphorylation kinetics in situ and provides insights into LCK activation dynamics.

    更新日期:2017-10-30
  • Molecular analysis of PRC2 recruitment to DNA in chromatin and its inhibition by RNA
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-23
    Xueyin Wang, Richard D Paucek, Anne R Gooding, Zachary Z Brown, Eva J Ge, Tom W Muir, Thomas R Cech

    Molecular analysis of PRC2 recruitment to DNA in chromatin and its inhibition by RNA Nature Structural & Molecular Biology, Published online: 23 October 2017; doi:10.1038/nsmb.3487 Biochemical reconstitution of PRC2 interactions with chromatinized templates demonstrates that protein-free linker DNA dominates the PRC2-nucleosome interaction, while RNA inhibits binding.

    更新日期:2017-10-30
  • Molecular basis of lipid-linked oligosaccharide recognition and processing by bacterial oligosaccharyltransferase
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-23
    Maja Napiórkowska, Jérémy Boilevin, Tina Sovdat, Tamis Darbre, Jean-Louis Reymond, Markus Aebi, Kaspar P Locher

    Molecular basis of lipid-linked oligosaccharide recognition and processing by bacterial oligosaccharyltransferase Nature Structural & Molecular Biology, Published online: 23 October 2017; doi:10.1038/nsmb.3491 The crystal structure of the single-subunit oligosaccharyltransferase PglB in complex with acceptor peptide and a synthetic lipid-linked oligosaccharide analog reveals a key intermediate in the reaction mechanism.

    更新日期:2017-10-30
  • Dynamic regulation of CD28 conformation and signaling by charged lipids and ions
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-23
    Wei Yang, Weiling Pan, Shuokai Chen, Nicola Trendel, Shutan Jiang, Feng Xiao, Manman Xue, Wei Wu, Zeli Peng, Xiaoxi Li, Hongbin Ji, Xiaolong Liu, Hai Jiang, Haopeng Wang, Hongbin Shen, Omer Dushek, Hua Li, Chenqi Xu

    Dynamic regulation of CD28 conformation and signaling by charged lipids and ions Nature Structural & Molecular Biology, Published online: 23 October 2017; doi:10.1038/nsmb.3489 CD28 signaling motifs are sequestered within the membrane via interactions with phospholipids. TCR activation increases the local Ca2+ concentration, which disrupts CD28-lipid interactions.

    更新日期:2017-10-30
  • Histone propionylation is a mark of active chromatin
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-23
    Adam F Kebede, Anna Nieborak, Lara Zorro Shahidian, Stephanie Le Gras, Florian Richter, Diana Aguilar Gómez, Marijke P Baltissen, Gergo Meszaros, Helena de Fatima Magliarelli, Aaron Taudt, Raphael Margueron, Maria Colomé-Tatché, Romeo Ricci, Sylvain Daujat, Michiel Vermeulen, Gerhard Mittler, Robert Schneider

    Histone propionylation is a mark of active chromatin Nature Structural & Molecular Biology, Published online: 23 October 2017; doi:10.1038/nsmb.3490 Histone H3 lysine 14 is propionylated and butyrylated in vivo in a metabolic-state-dependent manner and these modifications promote high levels of transcription.

    更新日期:2017-10-30
  • Telomeric TERB1–TRF1 interaction is crucial for male meiosis
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-30
    Juanjuan Long, Chenhui Huang, Yanyan Chen, Ying Zhang, Shaohua Shi, Ligang Wu, Yie Liu, Chengyu Liu, Jian Wu, Ming Lei

    Telomeric TERB1–TRF1 interaction is crucial for male meiosis Nature Structural & Molecular Biology, Published online: 30 October 2017; doi:10.1038/nsmb.3496 Disrupting the interaction between telomere protein TRF1 with meiosis-specific protein TERB1 impairs the pairing of X and Y chromosomes via their telomere-adjacent pseudoautosomal regions in pachytene, leading to spermatocyte apoptosis and male infertility in mice.

    更新日期:2017-10-30
  • Dissecting the telomere–inner nuclear membrane interface formed in meiosis
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-30
    Devon F Pendlebury, Yasuhiro Fujiwara, Valerie M Tesmer, Eric M Smith, Hiroki Shibuya, Yoshinori Watanabe, Jayakrishnan Nandakumar

    Dissecting the telomere–inner nuclear membrane interface formed in meiosis Nature Structural & Molecular Biology, Published online: 30 October 2017; doi:10.1038/nsmb.3493 Structural and functional analyses of human TRF1 in complex with meiosis-specific protein TERB1 reveal the basis for telomere tethering to the inner nuclear membrane and offer insight into the mechanism of dissociation in late pachytene.

    更新日期:2017-10-30
  • Preribosomes escaping from the nucleus are caught during translation by cytoplasmic quality control
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-30
    Anshuk Sarkar, Matthias Thoms, Clara Barrio-Garcia, Emma Thomson, Dirk Flemming, Roland Beckmann, Ed Hurt

    Preribosomes escaping from the nucleus are caught during translation by cytoplasmic quality control Nature Structural & Molecular Biology, Published online: 30 October 2017; doi:10.1038/nsmb.3495 Abnormal pre-60S particles are able to escape nuclear quality control and join mature 40S subunits to catalyze cytoplasmic protein synthesis, but the resulting translation defects trigger the cytoplasmic surveillance machineries RQC and the Ski-exosome.

    更新日期:2017-10-30
  • Encoding optical control in LCK kinase to quantitatively investigate its activity in live cells
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-30
    Ardiyanto Liaunardy-Jopeace, Ben L Murton, Mohan Mahesh, Jason W Chin, John R James

    Encoding optical control in LCK kinase to quantitatively investigate its activity in live cells Nature Structural & Molecular Biology, Published online: 30 October 2017; doi:10.1038/nsmb.3492 Engineering an LCK mutant, in which an active-site lysine is replaced by a photocaged equivalent via genetic code expansion, allows quantitation of phosphorylation kinetics in situ and provides insights into LCK activation dynamics.

    更新日期:2017-10-30
  • Molecular analysis of PRC2 recruitment to DNA in chromatin and its inhibition by RNA
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-23
    Xueyin Wang, Richard D Paucek, Anne R Gooding, Zachary Z Brown, Eva J Ge, Tom W Muir, Thomas R Cech

    Molecular analysis of PRC2 recruitment to DNA in chromatin and its inhibition by RNA Nature Structural & Molecular Biology, Published online: 23 October 2017; doi:10.1038/nsmb.3487 Biochemical reconstitution of PRC2 interactions with chromatinized templates demonstrates that protein-free linker DNA dominates the PRC2-nucleosome interaction, while RNA inhibits binding.

    更新日期:2017-10-30
  • Molecular basis of lipid-linked oligosaccharide recognition and processing by bacterial oligosaccharyltransferase
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-23
    Maja Napiórkowska, Jérémy Boilevin, Tina Sovdat, Tamis Darbre, Jean-Louis Reymond, Markus Aebi, Kaspar P Locher

    Molecular basis of lipid-linked oligosaccharide recognition and processing by bacterial oligosaccharyltransferase Nature Structural & Molecular Biology, Published online: 23 October 2017; doi:10.1038/nsmb.3491 The crystal structure of the single-subunit oligosaccharyltransferase PglB in complex with acceptor peptide and a synthetic lipid-linked oligosaccharide analog reveals a key intermediate in the reaction mechanism.

    更新日期:2017-10-30
  • Dynamic regulation of CD28 conformation and signaling by charged lipids and ions
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-23
    Wei Yang, Weiling Pan, Shuokai Chen, Nicola Trendel, Shutan Jiang, Feng Xiao, Manman Xue, Wei Wu, Zeli Peng, Xiaoxi Li, Hongbin Ji, Xiaolong Liu, Hai Jiang, Haopeng Wang, Hongbin Shen, Omer Dushek, Hua Li, Chenqi Xu

    Dynamic regulation of CD28 conformation and signaling by charged lipids and ions Nature Structural & Molecular Biology, Published online: 23 October 2017; doi:10.1038/nsmb.3489 CD28 signaling motifs are sequestered within the membrane via interactions with phospholipids. TCR activation increases the local Ca2+ concentration, which disrupts CD28-lipid interactions.

    更新日期:2017-10-30
  • Histone propionylation is a mark of active chromatin
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 2017-10-23
    Adam F Kebede, Anna Nieborak, Lara Zorro Shahidian, Stephanie Le Gras, Florian Richter, Diana Aguilar Gómez, Marijke P Baltissen, Gergo Meszaros, Helena de Fatima Magliarelli, Aaron Taudt, Raphael Margueron, Maria Colomé-Tatché, Romeo Ricci, Sylvain Daujat, Michiel Vermeulen, Gerhard Mittler, Robert Schneider

    Histone propionylation is a mark of active chromatin Nature Structural & Molecular Biology, Published online: 23 October 2017; doi:10.1038/nsmb.3490 Histone H3 lysine 14 is propionylated and butyrylated in vivo in a metabolic-state-dependent manner and these modifications promote high levels of transcription.

    更新日期:2017-10-30
  • Class 2 CRISPR–Cas RNA-guided endonucleases: Swiss Army knives of genome editing
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 
    Stefano Stella, Pablo Alcón, Guillermo Montoya

    Class 2 CRISPR–Cas RNA-guided endonucleases: Swiss Army knives of genome editing Nature Structural & Molecular Biology, Published online: 16 October 2017; doi:10.1038/nsmb.3486 This review highlights recent mechanistic insights into the CRISPR class 2 type V enzymes Cpf1 and C2c1, which are crucial for improving these genome engineering tools and expanding the genomic editing space.

    更新日期:2017-10-16
  • Class 2 CRISPR–Cas RNA-guided endonucleases: Swiss Army knives of genome editing
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 
    Stefano Stella, Pablo Alcón, Guillermo Montoya

    Class 2 CRISPR–Cas RNA-guided endonucleases: Swiss Army knives of genome editing Nature Structural & Molecular Biology, Published online: 16 October 2017; doi:10.1038/nsmb.3486 This review highlights recent mechanistic insights into the CRISPR class 2 type V enzymes Cpf1 and C2c1, which are crucial for improving these genome engineering tools and expanding the genomic editing space.

    更新日期:2017-10-16
  • MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 
    Melanija Posavec Marjanović, Sarah Hurtado-Bagès, Maximilian Lassi, Vanesa Valero, Roberto Malinverni, Hélène Delage, Miriam Navarro, David Corujo, Iva Guberovic, Julien Douet, Pau Gama-Perez, Pablo M Garcia-Roves, Ivan Ahel, Andreas G Ladurner, Oscar Yanes, Philippe Bouvet, Mònica Suelves, Raffaele Teperino, J Andrew Pospisilik, Marcus Buschbeck

    Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD+-derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation. Through direct binding, macroH2A1.1 inhibits basal poly-ADP ribose polymerase 1 (PARP-1) activity and thus reduces nuclear NAD+ consumption. The resultant accumulation of the NAD+ precursor NMN allows for maintenance of mitochondrial NAD+ pools that are critical for respiration. Our data indicate that macroH2A1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD+ consumption and establishing a buffer of NAD+ precursors in differentiated cells.

    更新日期:2017-10-11
  • A structural model for microtubule minus-end recognition and protection by CAMSAP proteins
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 
    Joseph Atherton, Kai Jiang, Marcel M Stangier, Yanzhang Luo, Shasha Hua, Klaartje Houben, Jolien J E van Hooff, Agnel-Praveen Joseph, Guido Scarabelli, Barry J Grant, Anthony J Roberts, Maya Topf, Michel O Steinmetz, Marc Baldus, Carolyn A Moores, Anna Akhmanova

    CAMSAP and Patronin family members regulate microtubule minus-end stability and localization and thus organize noncentrosomal microtubule networks, which are essential for cell division, polarization and differentiation. Here, we found that the CAMSAP C-terminal CKK domain is widely present among eukaryotes and autonomously recognizes microtubule minus ends. Through a combination of structural approaches, we uncovered how mammalian CKK binds between two tubulin dimers at the interprotofilament interface on the outer microtubule surface. In vitro reconstitution assays combined with high-resolution fluorescence microscopy and cryo-electron tomography suggested that CKK preferentially associates with the transition zone between curved protofilaments and the regular microtubule lattice. We propose that minus-end-specific features of the interprotofilament interface at this site serve as the basis for CKK's minus-end preference. The steric clash between microtubule-bound CKK and kinesin motors explains how CKK protects microtubule minus ends against kinesin-13-induced depolymerization and thus controls the stability of free microtubule minus ends.

    更新日期:2017-10-11
  • Architectural alterations of the fission yeast genome during the cell cycle
    Nat. Struct. Mol. Biol. (IF 12.595) Pub Date : 
    Hideki Tanizawa, Kyoung-Dong Kim, Osamu Iwasaki, Ken-ichi Noma

    Eukaryotic genomes are highly ordered through various mechanisms, including topologically associating domain (TAD) organization. We employed an in situ Hi-C approach to follow the 3D organization of the fission yeast genome during the cell cycle. We demonstrate that during mitosis, large domains of 300 kb–1 Mb are formed by condensin. This mitotic domain organization does not suddenly dissolve, but gradually diminishes until the next mitosis. By contrast, small domains of 30–40 kb that are formed by cohesin are relatively stable across the cell cycle. Condensin and cohesin mediate long- and short-range contacts, respectively, by bridging their binding sites, thereby forming the large and small domains. These domains are inversely regulated during the cell cycle but assemble independently. Our study describes the chromosomal oscillation between the formation and decay phases of the large and small domains, and we predict that the condensin-mediated domains serve as chromosomal compaction units.

    更新日期:2017-10-11
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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