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Yeast PI31 inhibits the proteasome by a direct multisite mechanism Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-08-04 Shaun Rawson, Richard M. Walsh, Benjamin Velez, Helena M. Schnell, Fenglong Jiao, Marie Blickling, Jessie Ang, Meera K. Bhanu, Lan Huang, John Hanna
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Mechanism of client selection by the protein quality-control factor UBE2O Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-08-01 Matthew C. J. Yip, Samantha F. Sedor, Sichen Shao
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Proteasome-dependent truncation of the negative heterochromatin regulator Epe1 mediates antifungal resistance Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-25 Imtiyaz Yaseen, Sharon A. White, Sito Torres-Garcia, Christos Spanos, Marcel Lafos, Elisabeth Gaberdiel, Rebecca Yeboah, Meriem El Karoui, Juri Rappsilber, Alison L. Pidoux, Robin C. Allshire
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Structure of the metastatic factor P-Rex1 reveals a two-layered autoinhibitory mechanism Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-21 Yong-Gang Chang, Christopher J. Lupton, Charles Bayly-Jones, Alastair C. Keen, Laura D’Andrea, Christina M. Lucato, Joel R. Steele, Hari Venugopal, Ralf B. Schittenhelm, James C. Whisstock, Michelle L. Halls, Andrew M. Ellisdon
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Coupling of distant ATPase domains in the circadian clock protein KaiC Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-21 Jeffrey A. Swan, Colby R. Sandate, Archana G. Chavan, Alfred M. Freeberg, Diana Etwaru, Dustin C. Ernst, Joseph G. Palacios, Susan S. Golden, Andy LiWang, Gabriel C. Lander, Carrie L. Partch
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Structurally derived universal mechanism for the catalytic cycle of the tail-anchored targeting factor Get3 Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-18 Michelle Y. Fry, Vladimíra Najdrová, Ailiena O. Maggiolo, Shyam M. Saladi, Pavel Doležal, William M. Clemons
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Reeling it in: how DNA topology drives loop extrusion by condensin Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-14 Domenic N. Narducci, Anders S. Hansen
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The band 3–ankyrin multiprotein complex comes in from the cold Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-14 Ashley M. Toye
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Architecture of the human erythrocyte ankyrin-1 complex Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-14 Francesca Vallese, Kookjoo Kim, Laura Y. Yen, Jake D. Johnston, Alex J. Noble, Tito Calì, Oliver Biggs Clarke
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Condensin-driven loop extrusion on supercoiled DNA Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-14 Eugene Kim, Alejandro Martin Gonzalez, Biswajit Pradhan, Jaco van der Torre, Cees Dekker
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Kinetic principles underlying pioneer function of GAGA transcription factor in live cells Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-14 Xiaona Tang, Taibo Li, Sheng Liu, Jan Wisniewski, Qinsi Zheng, Yikang Rong, Luke D. Lavis, Carl Wu
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Inactive and active state structures template selective tools for the human 5-HT5A receptor Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-14 Shicheng Zhang, He Chen, Chengwei Zhang, Ying Yang, Petr Popov, Jing Liu, Brian E. Krumm, Can Cao, Kuglae Kim, Yan Xiong, Vsevolod Katritch, Brian K. Shoichet, Jian Jin, Jonathan F. Fay, Bryan L. Roth
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Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-14 Thomas J. McCorvie, Paula M. Loria, Meihua Tu, Seungil Han, Leela Shrestha, D. Sean Froese, Igor M. Ferreira, Allison P. Berg, Wyatt W. Yue
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BIDding on PROTACs in an era of antibiotic resistance. Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-14 Sara Osman
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Parkinson's disease risk protein TMEM175 keeps lysosomes running on a proton leak. Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-12 Carolina N Perdigoto
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Structural insight into apelin receptor-G protein stoichiometry Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-11 Yang Yue, Lier Liu, Li-Jie Wu, Yiran Wu, Ling Wang, Fei Li, Junlin Liu, Gye-Won Han, Bo Chen, Xi Lin, Rebecca L. Brouillette, Émile Breault, Jean-Michel Longpré, Songting Shi, Hui Lei, Philippe Sarret, Raymond C. Stevens, Michael A. Hanson, Fei Xu
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Author Correction: Plasticity in ligand recognition at somatostatin receptors. Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-08 Michael J Robertson,Justin G Meyerowitz,Ouliana Panova,Kenneth Borrelli,Georgios Skiniotis
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Structural basis for inhibition and regulation of a chitin synthase from Candida albicans Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-07-04 Zhenning Ren, Abhishek Chhetri, Ziqiang Guan, Yang Suo, Kenichi Yokoyama, Seok-Yong Lee
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Telomeric 8-oxo-guanine drives rapid premature senescence in the absence of telomere shortening Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-06-30 Ryan P. Barnes, Mariarosaria de Rosa, Sanjana A. Thosar, Ariana C. Detwiler, Vera Roginskaya, Bennett Van Houten, Marcel P. Bruchez, Jacob Stewart-Ornstein, Patricia L. Opresko
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Fatty acid transporter MFSD2A is a multifunctional gatekeeper in brain and placenta Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-06-16 Justin D. Walter, Sille Remm, Markus A. Seeger
MFSD2A mediates uptake of the essential fatty acid DHA across the blood–brain barrier. Separately, via interactions with syncytin-2, MFSD2A contributes to the formation of the mother–fetus placental boundary. Cryo-EM analysis of a human MFSD2A–syncytin-2 complex provides new insights into how MFSD2A performs these dual roles.
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Rhodopsin-bestrophin fusion proteins from unicellular algae form gigantic pentameric ion channels Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-06-16 Andrey Rozenberg, Igor Kaczmarczyk, Donna Matzov, Johannes Vierock, Takashi Nagata, Masahiro Sugiura, Kota Katayama, Yuma Kawasaki, Masae Konno, Yujiro Nagasaka, Mako Aoyama, Ishita Das, Efrat Pahima, Jonathan Church, Suliman Adam, Veniamin A. Borin, Ariel Chazan, Sandra Augustin, Jonas Wietek, Julien Dine, Yoav Peleg, Akira Kawanabe, Yuichiro Fujiwara, Ofer Yizhar, Mordechai Sheves, Igor Schapiro
Many organisms sense light using rhodopsins, photoreceptive proteins containing a retinal chromophore. Here we report the discovery, structure and biophysical characterization of bestrhodopsins, a microbial rhodopsin subfamily from marine unicellular algae, in which one rhodopsin domain of eight transmembrane helices or, more often, two such domains in tandem, are C-terminally fused to a bestrophin
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Structural insights into the lysophospholipid brain uptake mechanism and its inhibition by syncytin-2 Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-06-16 Maria Martinez-Molledo, Emmanuel Nji, Nicolas Reyes
Brain development and function require uptake of essential omega-3 fatty acids in the form of lysophosphatidylcholine via major-facilitator superfamily transporter MFSD2A, a potential pharmaceutical target to modulate blood–brain barrier (BBB) permeability. MFSD2A is also the receptor of endogenous retroviral envelope syncytin-2 (SYNC2) in human placenta, where it mediates cell–cell fusion and formation
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Building regulatory landscapes reveals that an enhancer can recruit cohesin to create contact domains, engage CTCF sites and activate distant genes Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-06-16 Niels J. Rinzema, Konstantinos Sofiadis, Sjoerd J. D. Tjalsma, Marjon J. A. M. Verstegen, Yuva Oz, Christian Valdes-Quezada, Anna-Karina Felder, Teodora Filipovska, Stefan van der Elst, Zaria de Andrade dos Ramos, Ruiqi Han, Peter H. L. Krijger, Wouter de Laat
Developmental gene expression is often controlled by distal regulatory DNA elements called enhancers. Distant enhancer action is restricted to structural chromosomal domains that are flanked by CTCF-associated boundaries and formed through cohesin chromatin loop extrusion. To better understand how enhancers, genes and CTCF boundaries together form structural domains and control expression, we used
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Smc3 acetylation, Pds5 and Scc2 control the translocase activity that establishes cohesin-dependent chromatin loops Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-06-16 Nathalie Bastié, Christophe Chapard, Lise Dauban, Olivier Gadal, Frédéric Beckouët, Romain Koszul
Cohesin is a DNA translocase that is instrumental in the folding of the genome into chromatin loops, with functional consequences on DNA-related processes. Chromatin loop length and organization likely depend on cohesin processivity, translocation rate and stability on DNA. Here, we investigate and provide a comprehensive overview of the roles of various cohesin regulators in tuning chromatin loop
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The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-06-16 Marjon S. van Ruiten, Démi van Gent, Ángela Sedeño Cacciatore, Astrid Fauster, Laureen Willems, Maarten L. Hekkelman, Liesbeth Hoekman, Maarten Altelaar, Judith H. I. Haarhuis, Thijn R. Brummelkamp, Elzo de Wit, Benjamin D. Rowland
Cohesin structures the genome through the formation of chromatin loops and by holding together the sister chromatids. The acetylation of cohesin’s SMC3 subunit is a dynamic process that involves the acetyltransferase ESCO1 and deacetylase HDAC8. Here we show that this cohesin acetylation cycle controls the three-dimensional genome in human cells. ESCO1 restricts the length of chromatin loops, and of
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Screening thousands of transcribed coding and non-coding regions reveals sequence determinants of RNA polymerase II elongation potential Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-06-09 Hanneke Vlaming, Claudia A. Mimoso, Andrew R. Field, Benjamin J. E. Martin, Karen Adelman
Precise regulation of transcription by RNA polymerase II (RNAPII) is critical for organismal growth and development. However, what determines whether an engaged RNAPII will synthesize a full-length transcript or terminate prematurely is poorly understood. Notably, RNAPII is far more susceptible to termination when transcribing non-coding RNAs than when synthesizing protein-coding mRNAs, but the mechanisms
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Structure, dynamics and assembly of the ankyrin complex on human red blood cell membrane Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-06-02 Xian Xia, Shiheng Liu, Z. Hong Zhou
The cytoskeleton of a red blood cell (RBC) is anchored to the cell membrane by the ankyrin complex. This complex is assembled during RBC genesis and comprises primarily band 3, protein 4.2 and ankyrin, whose mutations contribute to numerous human inherited diseases. High-resolution structures of the ankyrin complex have been long sought-after to understand its assembly and disease-causing mutations
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Quaternary structure independent folding of voltage-gated ion channel pore domain subunits Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-06-02 Cristina Arrigoni, Marco Lolicato, David Shaya, Ahmed Rohaim, Felix Findeisen, Lam-Kiu Fong, Claire M. Colleran, Pawel Dominik, Sangwoo S. Kim, Jonathan P. Schuermann, William F. DeGrado, Michael Grabe, Anthony A. Kossiakoff, Daniel L. Minor
Every voltage-gated ion channel (VGIC) has a pore domain (PD) made from four subunits, each comprising an antiparallel transmembrane helix pair bridged by a loop. The extent to which PD subunit structure requires quaternary interactions is unclear. Here, we present crystal structures of a set of bacterial voltage-gated sodium channel (BacNaV) ‘pore only’ proteins that reveal a surprising collection
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Binding NEMO: Liquid-liquid phase separation captures immune regulator. Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-06-01 Sara Osman
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Extended and exposed enhancer RNAs activate transcription. Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-06-01 Sara Osman
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Identifying amyloid-related diseases by mapping mutations in low-complexity protein domains to pathologies Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-05-30 Kevin A. Murray, Michael P. Hughes, Carolyn J. Hu, Michael R. Sawaya, Lukasz Salwinski, Hope Pan, Samuel W. French, Paul M. Seidler, David S. Eisenberg
Proteins including FUS, hnRNPA2, and TDP-43 reversibly aggregate into amyloid-like fibrils through interactions of their low-complexity domains (LCDs). Mutations in LCDs can promote irreversible amyloid aggregation and disease. We introduce a computational approach to identify mutations in LCDs of disease-associated proteins predicted to increase propensity for amyloid aggregation. We identify several
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Structural insights into binding of therapeutic channel blockers in NMDA receptors Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-05-30 Tsung-Han Chou, Max Epstein, Kevin Michalski, Eve Fine, Philip C. Biggin, Hiro Furukawa
Excitatory signaling mediated by N-methyl-d-aspartate receptor (NMDAR) is critical for brain development and function, as well as for neurological diseases and disorders. Channel blockers of NMDARs are of medical interest owing to their potential for treating depression, Alzheimer’s disease, and epilepsy. However, precise mechanisms underlying binding and channel blockade have remained limited owing
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Mammalian PERIOD2 regulates H2A.Z incorporation in chromatin to orchestrate circadian negative feedback Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-05-23 Kevin Tartour, Francesca Andriani, Eric G. Folco, Dominika Letkova, Raphael Schneider, Isahak Saidi, Tomoki Sato, Patrick-Simon Welz, Salvador Aznar Benitah, Cédric Allier, Kiran Padmanabhan
Mammalian circadian oscillators are built on a feedback loop in which the activity of the transcription factor CLOCK–BMAL1 is repressed by the PER–CRY complex. Here, we show that murine Per−/− fibroblasts display aberrant nucleosome occupancy around transcription start sites (TSSs) and at promoter-proximal and distal CTCF sites due to impaired histone H2A.Z deposition. Knocking out H2A.Z mimicked the
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Allosteric regulation controls actin-bundling properties of human plastins Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-05-19 Christopher L. Schwebach, Elena Kudryashova, Richa Agrawal, Weili Zheng, Edward H. Egelman, Dmitri S. Kudryashov
Plastins/fimbrins are conserved actin-bundling proteins contributing to motility, cytokinesis and other cellular processes by organizing strikingly different actin assemblies as in aligned bundles and branched networks. We propose that this ability of human plastins stems from an allosteric communication between their actin-binding domains (ABD1/2) engaged in a tight spatial association. Here we show
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Histone H1 binding to nucleosome arrays depends on linker DNA length and trajectory Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-05-17 Marco Dombrowski, Maik Engeholm, Christian Dienemann, Svetlana Dodonova, Patrick Cramer
Throughout the genome, nucleosomes often form regular arrays that differ in nucleosome repeat length (NRL), occupancy of linker histone H1 and transcriptional activity. Here, we report cryo-EM structures of human H1-containing tetranucleosome arrays with four physiologically relevant NRLs. The structures show a zig-zag arrangement of nucleosomes, with nucleosomes 1 and 3 forming a stack. H1 binding
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A look under the hood of the machine that makes cilia beat Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-05-16 Elena A. Zehr, Antonina Roll-Mecak
The central apparatus regulates the beating of motile cilia. High-resolution structures of the almost complete central apparatus are now reported in two separate studies, shedding light on the mechanism of ciliary beating and marking a new era in our molecular understanding of cilia architecture and function.
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Cryo-EM structure of an active central apparatus Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-05-16 Long Han, Qinhui Rao, Renbin Yang, Yue Wang, Pengxin Chai, Yong Xiong, Kai Zhang
Accurately regulated ciliary beating in time and space is critical for diverse cellular activities, which impact the survival and development of nearly all eukaryotic species. An essential beating regulator is the conserved central apparatus (CA) of motile cilia, composed of a pair of microtubules (C1 and C2) associated with hundreds of protein subunits per repeating unit. It is largely unclear how
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Ciliary central apparatus structure reveals mechanisms of microtubule patterning Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-05-16 Miao Gui, Xiangli Wang, Susan K. Dutcher, Alan Brown, Rui Zhang
A pair of extensively modified microtubules form the central apparatus (CA) of the axoneme of most motile cilia, where they regulate ciliary motility. The external surfaces of both CA microtubules are patterned asymmetrically with large protein complexes that repeat every 16 or 32 nm. The composition of these projections and the mechanisms that establish asymmetry and longitudinal periodicity are unknown
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Cryo-EM structure of the human CST–Polα/primase complex in a recruitment state Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-05-16 Sarah W. Cai, John C. Zinder, Vladimir Svetlov, Martin W. Bush, Evgeny Nudler, Thomas Walz, Titia de Lange
The CST–Polα/primase complex is essential for telomere maintenance and functions to counteract resection at double-strand breaks. We report a 4.6-Å resolution cryo-EM structure of human CST–Polα/primase, captured prior to catalysis in a recruitment state stabilized by chemical cross-linking. Our structure reveals an evolutionarily conserved interaction between the C-terminal domain of the catalytic
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The HMCES DNA-protein cross-link functions as an intermediate in DNA interstrand cross-link repair Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-05-09 Daniel R. Semlow, Victoria A. MacKrell, Johannes C. Walter
The 5-hydroxymethylcytosine binding, embryonic stem-cell-specific (HMCES) protein forms a covalent DNA-protein cross-link (DPC) with abasic (AP) sites in single-stranded DNA, and the resulting HMCES-DPC is thought to suppress double-strand break formation in S phase. However, the dynamics of HMCES cross-linking and whether any DNA repair pathways normally include an HMCES-DPC intermediate remain unknown
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Reshuffling chromatin: how the human chromatin remodeler PBAF recognizes nucleosomes. Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-05-01 Sara Osman
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TALEDs complete the toolkit for editing human mitochondrial DNA. Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-05-01 Carolina N Perdigoto
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A 'Goldilocks' principle to activate transcription. Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-05-01 Beth Moorefield
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True-atomic-resolution insights into the structure and functional role of linear chains and low-barrier hydrogen bonds in proteins Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-04-28 Valentin Borshchevskiy, Kirill Kovalev, Ekaterina Round, Rouslan Efremov, Roman Astashkin, Gleb Bourenkov, Dmitry Bratanov, Taras Balandin, Igor Chizhov, Christian Baeken, Ivan Gushchin, Alexander Kuzmin, Alexey Alekseev, Andrey Rogachev, Dieter Willbold, Martin Engelhard, Ernst Bamberg, Georg Büldt, Valentin Gordeliy
Hydrogen bonds are fundamental to the structure and function of biological macromolecules and have been explored in detail. The chains of hydrogen bonds (CHBs) and low-barrier hydrogen bonds (LBHBs) were proposed to play essential roles in enzyme catalysis and proton transport. However, high-resolution structural data from CHBs and LBHBs is limited. The challenge is that their ‘visualization’ requires
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Single-stranded nucleic acid binding and coacervation by linker histone H1 Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-04-28 Rachel Leicher, Adewola Osunsade, Gabriella N. L. Chua, Sarah C. Faulkner, Andrew P. Latham, John W. Watters, Tuan Nguyen, Emily C. Beckwitt, Sophia Christodoulou-Rubalcava, Paul G. Young, Bin Zhang, Yael David, Shixin Liu
The H1 linker histone family is the most abundant group of eukaryotic chromatin-binding proteins. However, their contribution to chromosome structure and function remains incompletely understood. Here we use single-molecule fluorescence and force microscopy to directly visualize the behavior of H1 on various nucleic acid and nucleosome substrates. We observe that H1 coalesces around single-stranded
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Coordinated conformational changes in the V1 complex during V-ATPase reversible dissociation Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-04-25 Thamiya Vasanthakumar, Kristine A. Keon, Stephanie A. Bueler, Michael C. Jaskolka, John L. Rubinstein
Vacuolar-type ATPases (V-ATPases) are rotary enzymes that acidify intracellular compartments in eukaryotic cells. These multi-subunit complexes consist of a cytoplasmic V1 region that hydrolyzes ATP and a membrane-embedded VO region that transports protons. V-ATPase activity is regulated by reversible dissociation of the two regions, with the isolated V1 and VO complexes becoming autoinhibited on disassembly
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Snapshots of actin and tubulin folding inside the TRiC chaperonin Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-04-21 John J. Kelly, Dale Tranter, Els Pardon, Gamma Chi, Holger Kramer, Lotta Happonen, Kelly M. Knee, Jay M. Janz, Jan Steyaert, Christine Bulawa, Ville O. Paavilainen, Juha T. Huiskonen, Wyatt W. Yue
The integrity of a cell’s proteome depends on correct folding of polypeptides by chaperonins. The chaperonin TCP-1 ring complex (TRiC) acts as obligate folder for >10% of cytosolic proteins, including he cytoskeletal proteins actin and tubulin. Although its architecture and how it recognizes folding substrates are emerging from structural studies, the subsequent fate of substrates inside the TRiC chamber
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Author Correction: SETDB1-like MET-2 promotes transcriptional silencing and development independently of its H3K9me-associated catalytic activity Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-04-15 Colin E. Delaney,Stephen P. Methot,Veronique Kalck,Jan Seebacher,Daniel Hess,Susan M. Gasser,Jan Padeken
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A tweak and a peek: How Cas9 pries open double-stranded DNA to check its sequence Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-04-14 Selma Sinan, Rick Russell
The CRISPR–Cas enzyme Cas9 faces the challenge of identifying a specific nucleotide sequence within double-stranded DNA. New cryo-EM and biochemical studies show that in the earliest steps of binding, Cas9 bends the DNA and promotes unwinding of two base pairs, enabling it to efficiently scan the sequence of this critical region.
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Chromatin, stacked at the centromere Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-04-14 Katrina V. Good, Juan Ausió
Cryo-EM analysis reveals the mechanism by which chromatin is compacted at the centromere by the H3 histone variant CENP-N. Intriguingly, despite the structural differences between CENP-N and linker H1 histones, both appear to similarly compact higher-order nucleosome structures.
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CENP-N promotes the compaction of centromeric chromatin Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-04-14 Keda Zhou, Magdalena Gebala, Dustin Woods, Kousik Sundararajan, Garrett Edwards, Dan Krzizike, Jeff Wereszczynski, Aaron F. Straight, Karolin Luger
The histone variant CENP-A is the epigenetic determinant for the centromere, where it is interspersed with canonical H3 to form a specialized chromatin structure that nucleates the kinetochore. How nucleosomes at the centromere arrange into higher order structures is unknown. Here we demonstrate that the human CENP-A-interacting protein CENP-N promotes the stacking of CENP-A-containing mononucleosomes
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CRISPR–Cas9 bends and twists DNA to read its sequence Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-04-14 Joshua C. Cofsky, Katarzyna M. Soczek, Gavin J. Knott, Eva Nogales, Jennifer A. Doudna
In bacterial defense and genome editing applications, the CRISPR-associated protein Cas9 searches millions of DNA base pairs to locate a 20-nucleotide, guide RNA-complementary target sequence that abuts a protospacer-adjacent motif (PAM). Target capture requires Cas9 to unwind DNA at candidate sequences using an unknown ATP-independent mechanism. Here we show that Cas9 sharply bends and undertwists
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The partner-swapping sliding clamp loader exposed Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-04-11 David Jeruzalmi
Eukaryotes possess several clamp loaders comprising four common subunits and a fifth subunit unique to each complex. The RFC-A–E clamp loader loads the PCNA clamp at 3′-recessed structures for DNA replication. However, swapping a single subunit, Rad24, for RFC-A yields a clamp loader that prefers the 911 clamp and 5′-recessed DNA. Three new studies reveal detailed views of the clamp loading reaction
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DNA replication at high res Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-04-01 Beth Moorefield
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Synergistic activation of the insulin receptor via two distinct sites Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-03-31 Jie Li, Junhee Park, John P. Mayer, Kristofor J. Webb, Emiko Uchikawa, Jiayi Wu, Shun Liu, Xuewu Zhang, Michael H. B. Stowell, Eunhee Choi, Xiao-chen Bai
Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional roles of each binding event during IR activation remain unresolved. Here, we showed that IR incompletely saturated with insulin predominantly forms an asymmetric conformation and exhibits partial activation
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Short- and long-range interactions in the HIV-1 5′ UTR regulate genome dimerization and packaging Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-03-28 Liqing Ye, Anne-Sophie Gribling-Burrer, Patrick Bohn, Anuja Kibe, Charlene Börtlein, Uddhav B. Ambi, Shazeb Ahmad, Marco Olguin-Nava, Maureen Smith, Neva Caliskan, Max von Kleist, Redmond P. Smyth
RNA dimerization is the noncovalent association of two human immunodeficiency virus-1 (HIV-1) genomes. It is a conserved step in the HIV-1 life cycle and assumed to be a prerequisite for binding to the viral structural protein Pr55Gag during genome packaging. Here, we developed functional analysis of RNA structure-sequencing (FARS-seq) to comprehensively identify sequences and structures within the
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Structural basis of an endocytic checkpoint that primes the AP2 clathrin adaptor for cargo internalization Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-03-28 Edward A. Partlow, Kevin S. Cannon, Gunther Hollopeter, Richard W. Baker
Clathrin-mediated endocytosis (CME) is the main route of internalization from the plasma membrane. It is known that the heterotetrameric AP2 clathrin adaptor must open to simultaneously engage membrane and endocytic cargo, yet it is unclear how transmembrane cargos are captured to catalyze CME. Using cryogenic-electron microscopy, we discover a new way in which mouse AP2 can reorganize to expose membrane-
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Structure of the human GlcNAc-1-phosphotransferase αβ subunits reveals regulatory mechanism for lysosomal enzyme glycan phosphorylation Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-03-24 Hua Li, Wang-Sik Lee, Xiang Feng, Lin Bai, Benjamin C. Jennings, Lin Liu, Balraj Doray, William M. Canfield, Stuart Kornfeld, Huilin Li
Vertebrates use the mannose 6-phosphate (M6P)-recognition system to deliver lysosomal hydrolases to lysosomes. Key to this pathway is N-acetylglucosamine (GlcNAc)-1-phosphotransferase (PTase) that selectively adds GlcNAc-phosphate (P) to mannose residues of hydrolases. Human PTase is an α2β2γ2 heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates. Here
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Bound nucleotide can control the dynamic architecture of monomeric actin Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-03-24 Rustam Ali, Jacob A. Zahm, Michael K. Rosen
Polymerization of actin into cytoskeletal filaments is coupled to its bound adenine nucleotides. The mechanism by which nucleotide modulates actin functions has not been evident from analyses of ATP- and ADP-bound crystal structures of the actin monomer. We report that NMR chemical shift differences between the two forms are globally distributed. Furthermore, microsecond–millisecond motions are spread
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PARP inhibition impedes the maturation of nascent DNA strands during DNA replication Nat. Struct. Mol. Biol. (IF 18.361) Pub Date : 2022-03-24 Alina Vaitsiankova, Kamila Burdova, Margarita Sobol, Amit Gautam, Oldrich Benada, Hana Hanzlikova, Keith W. Caldecott
Poly(ADP-ribose) polymerase 1 (PARP1) is implicated in the detection and processing of unligated Okazaki fragments and other DNA replication intermediates, highlighting such structures as potential sources of genome breakage induced by PARP inhibition. Here, we show that PARP1 activity is greatly elevated in chicken and human S phase cells in which FEN1 nuclease is genetically deleted and is highest