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  • Cryo-EM structure of CLHM1 ion channel from Caenorhabditis elegans.
    Protein Sci. (IF 3.876) Pub Date : 2020-06-18
    Weixin Yang,Youwang Wang,Jianli Guo,Lingli He,Ye Zhou,Hui Zheng,Zhenfeng Liu,Ping Zhu,Xuejun C Zhang

    Calcium homeostasis modulators (CALHMs/CLHMs) comprise a family of pore‐forming protein complexes assembling into voltage‐gated, Ca2+‐sensitive, nonselective channels. These complexes contain an ion‐conduction pore sufficiently wide to permit the passing of ATP molecules serving as neurotransmitters. While their function and structure information is accumulating, the precise mechanisms of these channel

    更新日期:2020-06-30
  • Homodimerization of a glycoside hydrolase family GH1 β‐glucosidase suggests distinct activity of enzyme different states
    Protein Sci. (IF 3.876) Pub Date : 2020-06-29
    Felipe Akihiro Melo Otsuka; Rafael Siqueira Chagas; Vitor Medeiros Almeida; Sandro Roberto Marana

    In this work, we investigated how activity and oligomeric state are related in a purified GH1 β‐glucosidase from Spodoptera frugiperda (Sfβgly). Gel filtration chromatography coupled to a multiple angle light scattering detector allowed separation of the homodimer and monomer states and determination of the dimer dissociation constant (K D), which was in the micromolar range. Enzyme kinetic parameters

    更新日期:2020-06-29
  • These motors were made for walking.
    Protein Sci. (IF 3.876) Pub Date : 2020-05-29
    Byron Hunter,John S Allingham

    Kinesins are a diverse group of adenosine triphosphate (ATP)‐dependent motor proteins that transport cargos along microtubules (MTs) and change the organization of MT networks. Shared among all kinesins is a ~40 kDa motor domain that has evolved an impressive assortment of motility and MT remodeling mechanisms as a result of subtle tweaks and edits within its sequence. Several elegant studies of different

    更新日期:2020-06-27
  • The Long Form of pVHL is Artefactually Modified by Serine Protease Inhibitor AEBSF.
    Protein Sci. (IF 3.876) Pub Date : 2020-06-14
    Daniel Tarade,Shelley He,Jonathan St-Germain,Avi Petroff,Anya Murphy,Brian Raught,Michael Ohh

    von Hippel–Lindau protein (pVHL) is the tumor suppressor responsible for ubiquitylating the hypoxia‐inducible factor (HIF) family of transcription factors for degradation under normoxic conditions. There are two major pVHL isoforms with the shorter isoform (pVHL19) lacking the acidic domain present in the N‐terminus of the longer isoform (pVHL30). Although both isoforms can degrade HIF and suppress

    更新日期:2020-06-25
  • In This Issue
    Protein Sci. (IF 3.876) Pub Date : 2020-06-24

    1567 High‐resolution structures of transient receptor potential vanilloid channels: Unveiling a functionally diverse group of ion channels Mark K. van Goor, Leanne de Jager, Yifan Cheng and Jenny van der Wijst The transient receptor potential vanilloid (TRPV) family belongs to a large class of ion channels that are widely expressed and considered as key players in human physiology. Their activity is

    更新日期:2020-06-25
  • Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-17
    Youngchang Kim,Robert Jedrzejczak,Natalia I Maltseva,Mateusz Wilamowski,Michael Endres,Adam Godzik,Karolina Michalska,Andrzej Joachimiak

    Severe Acute Respiratory Syndrome coronavirus 2 (SARS‐CoV‐2) is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS‐CoVs and Middle East Respiratory Syndrome coronavirus (MERS‐CoVs), the detailed information about SARS‐CoV‐2 proteins structures and functions is urgently

    更新日期:2020-06-25
  • Two fatty acid-binding proteins expressed in the intestine interact differently with endocannabinoids.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-16
    May Poh Lai,Francine S Katz,Cédric Bernard,Judith Storch,Ruth E Stark

    Two different members of the fatty acid‐binding protein (FABP) family are found in enterocyte cells of the gastrointestinal system, namely liver‐type and intestinal fatty acid‐binding proteins (LFABP and IFABP, also called FABP1 and FABP2, respectively). Striking phenotypic differences have been observed in knockout mice for either protein, for example, high fat‐fed IFABP‐null mice remained lean, whereas

    更新日期:2020-06-25
  • Comparison of metal-bound and unbound structures of aminopeptidase B proteins from Escherichia coli and Yersinia pestis.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-19
    George Minasov,Matthew R Lam,Monica Rosas-Lemus,Joanna Sławek,Magdalena Woinska,Ivan G Shabalin,Ludmilla Shuvalova,Bernhard Ø Palsson,Adam Godzik,Wladek Minor,Karla J F Satchell

    Protein degradation by aminopeptidases is involved in bacterial responses to stress. Escherichia coli produces two metal‐dependent M17 family leucine aminopeptidases (LAPs), aminopeptidase A (PepA) and aminopeptidase B (PepB). Several structures have been solved for PepA as well as other bacterial M17 peptidases. Herein, we report the first structures of a PepB M17 peptidase. The E. coli PepB protein

    更新日期:2020-06-25
  • Oligomerization of a symmetric β-trefoil protein in response to folding nucleus perturbation.
    Protein Sci. (IF 3.876) Pub Date : 2020-05-03
    Connie A Tenorio,Joseph B Parker,Michael Blaber

    Gene duplication and fusion events in protein evolution are postulated to be responsible for the common protein folds exhibiting internal rotational symmetry. Such evolutionary processes can also potentially yield regions of repetitive primary structure. Repetitive primary structure offers the potential for alternative definitions of critical regions, such as the folding nucleus (FN). In principle

    更新日期:2020-06-25
  • Deuteration of nonexchangeable protons on proteins affects their thermal stability, side-chain dynamics, and hydrophobicity.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-30
    Parker J Nichols,Isaac Falconer,Aaron Griffin,Colin Mant,Robert Hodges,Christopher J McKnight,Beat Vögeli,Liliya Vugmeyster

    We have investigated the effect of deuteration of non‐exchangeable protons on protein global thermal stability, hydrophobicity, and local flexibility using well‐known thermostable model systems such as the villin headpiece subdomain (HP36) and the third immunoglobulin G‐binding domain of protein G (GB3). Reversed‐phase high‐performance liquid chromatography (RP‐HPLC) measurements as a function of temperature

    更新日期:2020-06-25
  • Structural and chemical trapping of flavin-oxide intermediates reveals substrate-directed reaction multiplicity.
    Protein Sci. (IF 3.876) Pub Date : 2020-05-03
    Kuan-Hung Lin,Syue-Yi Lyu,Hsien-Wei Yeh,Yi-Shan Li,Ning-Shian Hsu,Chun-Man Huang,Yung-Lin Wang,Hao-Wei Shih,Zhe-Chong Wang,Chang-Jer Wu,Tsung-Lin Li

    Though reactive flavin‐N5/C4α‐oxide intermediates can be spectroscopically profiled for some flavin‐assisted enzymatic reactions, their exact chemical configurations are hardly visualized. Structural systems biology and stable isotopic labelling techniques were exploited to correct this stereotypical view. Three transition‐like complexes, the α‐ketoacid…N5‐FMNox complex (I ), the FMNox‐N5‐aloxyl‐C′α−‐C4α+

    更新日期:2020-06-25
  • Chaperone action of a cofactor in protein folding.
    Protein Sci. (IF 3.876) Pub Date : 2020-05-08
    Chen Chen,Chiwook Park

    Previously, we have reported that ATP accelerates the folding and unfolding of Escherichia coli glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), which is a glycolytic enzyme utilizing NAD+ as a cofactor. Because ATP and NAD+ share the ADP moiety, we hypothesized that NAD+ also accelerates the folding of GAPDH and that the common structural motif between ATP and NAD+ is responsible for the chaperone

    更新日期:2020-06-25
  • High affinity between CREBBP/p300 and NCOA evolved in vertebrates.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-23
    Elin Karlsson,Amanda Lindberg,Eva Andersson,Per Jemth

    The interaction between the transcriptional coactivators CREBBP/p300 and NCOA is governed by two intrinsically disordered domains called NCBD and CID, respectively. The CID domain emerged within the NCOA protein in deuterostome animals (including vertebrates) after their split from the protostomes (molluscs, worms, and arthropods). However, it has not been clear at which point a high affinity interaction

    更新日期:2020-06-25
  • Harnessing Synthetic Biology to Enhance Heterologous Protein Expression.
    Protein Sci. (IF 3.876) Pub Date : 2020-06-22
    Shlomo Zarzhitsky,Alex Jiang,Elizabeth Stanley,Michael Hecht

    The ability to express heterologous proteins in microbial hosts is crucial for many areas of research and technology. In most cases, however, successful expression and purification of the desired protein requires fusion to another protein. To date, all fusion partners have been chosen from natural sequences, which evolved for other purposes, and may not be optimal fusion partners. However, the rise

    更新日期:2020-06-22
  • Progress toward Alzheimer's disease treatment: Leveraging the Achilles' heel of Aβ oligomers ?
    Protein Sci. (IF 3.876) Pub Date : 2020-06-21
    Jacques Fantini,Henri Chahinian,Nouara Yahi

    After three decades of false hopes and failures, a pipeline of therapeutic drugs that target the actual root cause of Alzheimer's disease is now available. Challenging the old paradigm that focused on β‐amyloid peptide (Aβ) aggregation in amyloid plaques, these compounds are designed to prevent the neurotoxicity of Aβ oligomers that form Ca2+ permeable pores in the membranes of brain cells. By triggering

    更新日期:2020-06-22
  • A mechanistic view of enzyme evolution.
    Protein Sci. (IF 3.876) Pub Date : 2020-06-19
    Gloria Yang,Charlotte Miton,Nobuhiko Tokuriki

    New enzyme functions often evolve through the recruitment and optimization of latent promiscuous activities. How do mutations alter the molecular architecture of enzymes to enhance their activities? Can we infer general mechanisms that are common to most enzymes, or does each enzyme require a unique optimization process? The ability to predict the location and type of mutations necessary to enhance

    更新日期:2020-06-19
  • (S)-4-Amino-5-phenoxypentanoate Designed as a Potential Selective Agonist of the Bacterial Transcription Factor GabR.
    Protein Sci. (IF 3.876) Pub Date : 2020-06-18
    Daniel S Catlin,Cory T Reidl,Thomas R Trzupek,Richard B Silverman,Brian Cannon,Daniel P Becker,Dali Liu

    Addressing molecular recognition in the context of evolution requires pursuing new molecular targets to enable the development of agonists or antagonists with new mechanisms of action. Disruption of transcriptional regulation through targeting transcription factors that regulate the expression of key enzymes in bacterial metabolism may provide a promising method for controlling the bacterial metabolic

    更新日期:2020-06-18
  • PyXlinkViewer: a flexible tool for visualisation of protein chemical crosslinking data within the PyMOL molecular graphics system.
    Protein Sci. (IF 3.876) Pub Date : 2020-06-18
    Bob Schiffrin,Sheena E Radford,David J Brockwell,Antonio N Calabrese

    Chemical crosslinking‐mass spectrometry (XL‐MS) is a valuable technique for gaining insights into protein structure and the organization of macromolecular complexes. XL‐MS data yields inter‐residue restraints that can be compared with high‐resolution structural data. Distances greater than the crosslinker spacer‐arm can reveal lowly‐populated “excited” states of proteins/protein assemblies, or crosslinks

    更新日期:2020-06-18
  • Solution Structure of zinc finger domain of human RNF144A ubiquitin ligase.
    Protein Sci. (IF 3.876) Pub Date : 2020-06-17
    Kazuhide Miyamoto,Kaori Migita,Kazuki Saito

    RNF144A is involved in protein ubiquitination and functions as ubiquitin‐protein ligase (E3) via its RING finger domain (RNF144A RING). RNF144A is associated with degradation of heat‐shock protein family A member 2 (HSPA2), which leads to the suppression of breast cancer cell proliferation. In this study, the solution structure of RNF144A RING was determined using nuclear magnetic resonance (NMR).

    更新日期:2020-06-18
  • Conserved Buried Water Molecules Enable the β-Trefoil Architecture.
    Protein Sci. (IF 3.876) Pub Date : 2020-06-15
    Michael Blaber

    Available high‐resolution crystal structures for the family of β‐trefoil proteins in the structural databank were queried for buried waters. Such waters were classified as either: 1) unique to a particular domain, family, or superfamily, or 2) conserved among all β‐trefoil folds. Three buried waters conserved among all β‐trefoil folds were identified. These waters are related by the threefold rotational

    更新日期:2020-06-15
  • Discriminating changes in protein structure using PTAD conjugation to tyrosine.
    Protein Sci. (IF 3.876) Pub Date : 2020-06-02
    Mahta Moinpour,Natalie K Barker,Lindsay E Guzman,John C Jewett,Paul R Langlais,Jacob C Schwartz

    Chemical modification of proteins has been crucial in engineering protein‐based therapies, targeted biopharmaceutics, molecular probes, and biomaterials. Here, we explore the use of a conjugation‐based approach to sense alternative conformational states in proteins. Tyrosine has both hydrophobic and hydrophilic qualities, thus allowing it to be positioned at protein surfaces, or binding interfaces

    更新日期:2020-06-02
  • Structure of cytochrome b5 unique to tardigrades.
    Protein Sci. (IF 3.876) Pub Date : 2020-06-01
    Yohta Fukuda,JeeEun Kim,Tsuyoshi Inoue

    Cytochrome b 5 is an essential electron transfer protein, which is ubiquitously found in living systems and involved in wide variety of biological processes. Tardigrades (also known as water bears), some of which are famous for desiccation resistance, have many proteins unique to them. Here, we report spectroscopic and structural characterization of a cytochrome b 5 like protein from one of the desiccation‐tolerant

    更新日期:2020-06-01
  • Design of a surrogate Anticalin protein directed against CD98hc for preclinical studies in mice.
    Protein Sci. (IF 3.876) Pub Date : 2020-05-28
    Friedrich-Christian Deuschle,André Schiefner,Corinna Brandt,Arne Skerra

    The human CD98 heavy chain (CD98hc) offers a promising biomedical target both for tumor therapy and for drug delivery to the brain. We have previously developed a cognate Anticalin protein with picomolar affinity and demonstrated its effectiveness in a xenograft animal model. Due to the lack of cross‐reactivity with the murine ortholog, we now report the development and X‐ray structural analysis of

    更新日期:2020-05-28
  • Introduction.
    Protein Sci. (IF 3.876) Pub Date : 2020-05-19
    Mary Munson

    1 CELLULAR DYNAMICS A glimpse inside of a eukaryotic cell reveals an amazing and beautiful world at the micro‐ and nano‐scale, which is crowded with components in constant motion (Figure 1). Cells are constantly growing, dividing, bringing in nutrients, and synthesizing new macromolecules and assembling them into complex structures and organelles, as well as transporting materials to the outside of

    更新日期:2020-05-19
  • In This Issue.
    Protein Sci. (IF 3.876) Pub Date : 2020-05-01

    1071 Structure, function, and biosynthesis of nickel–dependent enzymes Marila Alfano and Christine Cavazza Nickel was a key player in catalyst development. However, according to the nickel famine theory, the drastic diminution of nickel availability on earth would be correlated to the existence of only nine nickel enzymes in archaea, bacteria, plants and primitive eukaryotes, while no nickel enzyme

    更新日期:2020-04-27
  • Current developments in Coot for macromolecular model building of Electron Cryo-microscopy and Crystallographic Data.
    Protein Sci. (IF 3.876) Pub Date : 2020-03-02
    Ana Casañal,Bernhard Lohkamp,Paul Emsley

    Coot is a tool widely used for model building, refinement, and validation of macromolecular structures. It has been extensively used for crystallography and, more recently, improvements have been introduced to aid in cryo-EM model building and refinement, as cryo-EM structures with resolution ranging 2.5-4 A are now routinely available. Model building into these maps can be time-consuming and requires

    更新日期:2020-04-22
  • The mechanism of Single strand binding protein-RecG binding: Implications for SSB interactome function.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-17
    Wenfei Ding,Hui Yin Tan,Jia Xiang Zhang,Luke A Wilczek,Karin R Hsieh,Jeffrey A Mulkin,Piero R Bianco

    The Escherichia coli single-strand DNA binding protein (SSB) is essential to viability where it functions to regulate SSB interactome function. Here it binds to single-stranded DNA and to target proteins that comprise the interactome. The region of SSB that links these two essential protein functions is the intrinsically disordered linker. Key to linker function is the presence of three, conserved

    更新日期:2020-04-17
  • Toward a new picture of the living plasma membrane.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-16
    Joseph Mathew Kalappurakkal,Parijat Sil,Satyajit Mayor

    Our understanding of the plasma membrane structure has undergone a major change since the proposal of the fluid mosaic model of Singer and Nicholson in the 1970s. In this model, the membrane, composed of over thousand lipid and protein species, is organized as a well-equilibrated two-dimensional fluid. Here, the distribution of lipids is largely expected to reflect a multicomponent system, and proteins

    更新日期:2020-04-16
  • Insulin and epidermal growth factor receptor family members share parallel activation mechanisms.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-16
    Kathryn M Ferguson,Chun Hu,Mark A Lemmon

    Insulin receptor (IR) and the epidermal growth factor receptor (EGFR) were the first receptor tyrosine kinases (RTKs) to be studied in detail. Both are important clinical targets-in diabetes and cancer, respectively. They have unique extracellular domain compositions among RTKs, but share a common module with two ligand-binding leucine-rich-repeat (LRR)-like domains connected by a flexible cysteine-rich

    更新日期:2020-04-16
  • A cellular perspective of bias at G protein-coupled receptors.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-16
    Thomas J Fernandez,Monica De Maria,Braden T Lobingier

    G protein-coupled receptors (GPCRs) modulate cell function over short- and long-term timescales. GPCR signaling depends on biochemical parameters that define the what, when, and where of receptor function: what proteins mediate and regulate receptor signaling, where within the cell these interactions occur, and how long these interactions persist. These parameters can vary significantly depending on

    更新日期:2020-04-16
  • Characterization of CNPY5 and its family members.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-15
    Danny Schildknegt,Naomi Lodder,Abhinav Pandey,Maarten Egmond,Florentina Pena,Ineke Braakman,Peter van der Sluijs

    Characterization of CNPY5 and its family members Danny Schildknegt,1 Naomi Lodder,1 Abhinav Pandey,1 Maarten Egmond,2 Florentina Pena,1 Ineke Braakman,1 and Peter van der Sluijs1 1Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands and Membrane Biochemistry2Biophysics, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht

    更新日期:2020-04-15
  • Integrating structural and evolutionary data to interpret variation and pathogenicity in adapter protein complex 4.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-13
    John E Gadbery,Abin Abraham,Carli D Needle,Christopher Moth,Jonathan Sheehan,John A Capra,Lauren P Jackson

    Genetic variation in the membrane trafficking adapter protein complex 4 (AP-4) can result in pathogenic neurological phenotypes including microencephaly, spastic paraplegias, epilepsy, and other developmental defects. We lack molecular mechanisms responsible for impaired AP-4 function arising from genetic variation, because AP-4 remains poorly understood structurally. Here, we analyze patterns of AP-4

    更新日期:2020-04-13
  • Characterization of CaMKIIα holoenzyme stability.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-13
    Ana P Torres-Ocampo,Can Özden,Alexandra Hommer,Anne Gardella,Emily Lapinskas,Alfred Samkutty,Edward Esposito,Scott C Garman,Margaret M Stratton

    Ca2+ /calmodulin-dependent protein kinase II (CaMKII) is a Ser/Thr kinase necessary for long-term memory formation and other Ca2+ -dependent signaling cascades such as fertilization. Here, we investigated the stability of CaMKIIα using a combination of differential scanning calorimetry (DSC), X-ray crystallography, and mass photometry (MP). The kinase domain has a low thermal stability (apparent Tm

    更新日期:2020-04-13
  • Atg3 promotes Atg8 lipidation via altering lipid diffusion and rearrangement.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-10
    Shen Wang,Yun Li,Cong Ma

    Atg3-catalyzed transferring of Atg8 to phosphatidylethanolamine (PE) in the phagophore membrane is essential for autophagy. Previous studies have demonstrated that this process requires Atg3 to interact with the phagophore membrane via its N-terminal amphipathic helix. In this study, by using combined biochemical and biophysical approaches, our data showed that in addition to binding to the membranes

    更新日期:2020-04-10
  • Mapping p38α mitogen-activated protein kinase signaling by proximity-dependent labeling.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-07
    Emmanuel Prikas,Anne Poljak,Arne Ittner

    Mitogen-activated protein (MAP) kinase signaling is central to multiple cellular responses and processes. MAP kinase p38α is the best characterized member of the p38 MAP kinase family. Upstream factors and downstream targets of p38α have been identified in the past by conventional methods such as coimmunoprecipitation. However, a complete picture of its interaction partners and substrates in cells

    更新日期:2020-04-07
  • Structural and biochemical characterization of SADS-CoV papain-like protease 2.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-06
    Lu Wang,Weihua Hu,Chengpeng Fan

    Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel coronavirus that is involved in severe diarrhea disease in piglets, causing considerable agricultural and economic loss in China. The emergence of this new coronavirus increases the importance of understanding SADS-CoV as well as antivirals. Coronaviral proteases, including main proteases and papain-like proteases (PLP), are attractive

    更新日期:2020-04-06
  • X-ray crystal structure localizes the mechanism of inhibition of an IL-36R antagonist monoclonal antibody to interaction with Ig1 and Ig2 extra cellular domains.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-02
    Eric T Larson,Debra L Brennan,Eugene R Hickey,Raj Ganesan,Rachel Kroe-Barrett,Neil A Farrow

    Cellular signaling via binding of the cytokines IL‐36α, β, and γ along with binding of the accessory protein IL‐36RAcP, to their cognate receptor IL‐36R is believed to play a major role in epithelial and immune cell‐mediated inflammation responses. Antagonizing the signaling cascade that results from these binding events via a directed monoclonal antibody provides an opportunity to suppress such immune

    更新日期:2020-04-02
  • Integrative structure and function of the yeast exocyst complex.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-02
    Sai J Ganesan,Michael J Feyder,Ilan E Chemmama,Fei Fang,Michael P Rout,Brian T Chait,Yi Shi,Mary Munson,Andrej Sali

    Exocyst is an evolutionarily conserved hetero-octameric tethering complex that plays a variety of roles in membrane trafficking, including exocytosis, endocytosis, autophagy, cell polarization, cytokinesis, pathogen invasion, and metastasis. Exocyst serves as a platform for interactions between the Rab, Rho, and Ral small GTPases, SNARE proteins, and Sec1/Munc18 regulators that coordinate spatial and

    更新日期:2020-04-02
  • Purification and crystal structure of human ODA16: Implications for ciliary import of outer dynein arms by the intraflagellar transport machinery.
    Protein Sci. (IF 3.876) Pub Date : 2020-04-02
    Jiaolong Wang,Michael Taschner,Narcis A Petriman,Marie B Andersen,Jerome Basquin,Sagar Bhogaraju,Melanie Vetter,Stefanie Wachter,Anna Lorentzen,Esben Lorentzen

    Motile cilia protrude from cell surfaces and are necessary to create movement of cells and fluids in the body. At the molecular level, cilia contain several dynein molecular motor complexes including outer dynein arms (ODAs) that are attached periodically to the ciliary axoneme, where they hydrolyse ATP to create the force required for bending and motility of the cilium. ODAs are preassembled in the

    更新日期:2020-04-02
  • High-resolution structures of transient receptor potential vanilloid channels: Unveiling a functionally diverse group of ion channels.
    Protein Sci. (IF 3.876) Pub Date : 2020-03-31
    Mark K van Goor,Leanne de Jager,Yifan Cheng,Jenny van der Wijst

    Transient receptor potential vanilloid (TRPV) channels are part of the superfamily of TRP ion channels and play important roles in widespread physiological processes including both neuronal and non‐neuronal pathways. Various diseases such as skeletal abnormalities, chronic pain, and cancer are associated with dysfunction of a TRPV channel. In order to obtain full understanding of disease pathogenesis

    更新日期:2020-03-31
  • Cellular functions and intrinsic attributes of the ATP-binding Eps15 homology domain-containing proteins.
    Protein Sci. (IF 3.876) Pub Date : 2020-03-29
    Soumya Bhattacharyya,Thomas J Pucadyil

    Several cellular processes rely on a cohort of dedicated proteins that manage tubulation, fission, and fusion of membranes. A notably large number of them belong to the dynamin superfamily of proteins. Among them is the evolutionarily conserved group of ATP‐binding Eps15‐homology domain‐containing proteins (EHDs). In the two decades since their discovery, EHDs have been linked to a range of cellular

    更新日期:2020-03-29
  • The metastable states of proteins
    Protein Sci. (IF 3.876) Pub Date : 2020-03-29
    Debasish Kumar Ghosh; Akash Ranjan

    The intriguing process of protein folding comprises discrete steps that stabilize the protein molecules in different conformations. The metastable state of protein is represented by specific conformational characteristics, which place the protein in a local free energy minimum state of the energy landscape. The native‐to‐metastable structural transitions are governed by transient or long‐lived thermodynamic

    更新日期:2020-03-29
  • Identification and in silico bioinformatics analysis of PR10 proteins in cashew nut.
    Protein Sci. (IF 3.876) Pub Date : 2020-03-27
    Shanna Bastiaan-Net,Maria C Pina-Pérez,Bas J W Dekkers,Adrie H Westphal,Antoine H P America,Renata M C Ariëns,Nicolette W de Jong,Harry J Wichers,Jurriaan J Mes

    Proteins from cashew nut can elicit mild to severe allergic reactions. Three allergenic proteins have already been identified, and it is expected that additional allergens are present in cashew nut. pathogenesis‐related protein 10 (PR10) allergens from pollen have been found to elicit similar allergic reactions as those from nuts and seeds. Therefore, we investigated the presence of PR10 genes in cashew

    更新日期:2020-03-27
  • Three-dimensional organization of the cytoskeleton: A cryo-electron tomography perspective.
    Protein Sci. (IF 3.876) Pub Date : 2020-03-26
    Saikat Chakraborty,Marion Jasnin,Wolfgang Baumeister

    Traditionally, structures of cytoskeletal components have been studied ex situ, that is, with biochemically purified materials. There are compelling reasons to develop approaches to study them in situ in their native functional context. In recent years, cryo‐electron tomography emerged as a powerful method for visualizing the molecular organization of unperturbed cellular landscapes with the potential

    更新日期:2020-03-26
  • Ab initio folding of a trefoil-fold motif reveals structural similarity with a β-propeller blade motif.
    Protein Sci. (IF 3.876) Pub Date : 2020-03-25
    Connie A Tenorio,Liam M Longo,Joseph B Parker,Jihun Lee,Michael Blaber

    Many protein architectures exhibit evidence of internal rotational symmetry postulated to be the result of gene duplication/fusion events involving a primordial polypeptide motif. A common feature of such structures is a domain-swapped arrangement at the interface of the N- and C-termini motifs and postulated to provide cooperative interactions that promote folding and stability. De novo designed symmetric

    更新日期:2020-03-25
  • The function of histone lysine methylation related SET domain group proteins in plants.
    Protein Sci. (IF 3.876) Pub Date : 2020-03-19
    Huiyan Zhou,Yanhong Liu,Yuwei Liang,Dong Zhou,Shuifeng Li,Sue Lin,Heng Dong,Li Huang

    Histone methylation, which is mediated by the histone lysine (K) methyltransferases (HKMTases), is a mechanism associated with many pathways in eukaryotes. Most HKMTases have a conserved SET (Su(var) 3-9,E(z),Trithorax) domain, while the HKMTases with SET domains are called the SET domain group (SDG) proteins. In plants, only SDG proteins can work as HKMTases. In this review, we introduced the classification

    更新日期:2020-03-19
  • Engineering a human IgG2 antibody stable at low pH.
    Protein Sci. (IF 3.876) Pub Date : 2020-03-18
    Seiji Saito,Hiroshi Namisaki,Keiko Hiraishi,Nobuaki Takahashi,Shigeru Iida

    IgG2 subclass antibodies have unique properties that include low effector function and a rigid hinge region. Although some IgG2 subclasses have been clinically tested and approved for therapeutic use, they have a higher propensity than IgG1 for aggregation, which can curtail or abolish their biological activity and enhance their immunogenicity. In this regard, acid-induced aggregation of monoclonal

    更新日期:2020-03-18
  • A glimpse into the molecular mechanism of integral membrane proteins through hydrogen-deuterium exchange mass spectrometry.
    Protein Sci. (IF 3.876) Pub Date : 2020-03-14
    Chloe Martens,Argyris Politis

    Integral membrane proteins (IMPs) control countless fundamental biological processes and constitute the majority of drug targets. For this reason, uncovering their molecular mechanism of action has long been an intense field of research. They are, however, notoriously difficult to work with, mainly due to their localization within the heterogeneous of environment of the biological membrane and the

    更新日期:2020-03-14
  • Single-particle analysis of urea amidolyase reveals its molecular mechanism.
    Protein Sci. (IF 3.876) Pub Date : 2020-03-10
    Ying Liu,Bin Yuan,Liang Peng,Jing Zhao,Bin Cheng,Yuhua Huang,Xinxing Zheng,Yuerong Zhou,Song Xiang,Li Zhu,Yi Wu

    Urea amidolyase (UA), a bifunctional enzyme that is widely distributed in bacteria, fungi, algae, and plants, plays a pivotal role in the recycling of nitrogen in the biosphere. Its substrate urea is ultimately converted to ammonium, via successive catalysis at the C-terminal urea carboxylase (UC) domain and followed by the N-terminal allophanate hydrolyse (AH) domain. Although our previous studies

    更新日期:2020-03-10
  • Differences in stability and calcium sensitivity of the Ig domains in titin's N2A region.
    Protein Sci. (IF 3.876) Pub Date : 2020-03-07
    Colleen M Kelly,Sophia Manukian,Emily Kim,Matthew J Gage

    Titin is a large filamentous protein that spans half a sarcomere, from Z-disk to M-line. The N2A region within the titin molecule exists between the proximal immunoglobulin (Ig) region and the PEVK region and protein-protein interactions involving this region are required for normal muscle function. The N2A region consists of four Ig domains (I80-I83) with a 105 amino acid linker region between I80

    更新日期:2020-03-07
  • Mechanisms of negative membrane curvature sensing and generation by ESCRT III subunit Snf7.
    Protein Sci. (IF 3.876) Pub Date : 2020-03-06
    Binod Nepal,Aliasghar Sepehri,Themis Lazaridis

    Certain proteins have the propensity to bind to negatively curved membranes and generate negative membrane curvature. The mechanism of action of these proteins is much less studied and understood than those that sense and generate positive curvature. In this work, we use implicit membrane modeling to explore the mechanism of an important negative curvature sensing and generating protein: the main ESCRT

    更新日期:2020-03-06
  • Biochemical analysis of a sugar 4,6-dehydratase from Acanthamoeba polyphaga Mimivirus.
    Protein Sci. (IF 3.876) Pub Date : 2020-03-04
    Justin D Ferek,James B Thoden,Hazel M Holden

    The exciting discovery of the giant DNA Mimivirus in 2003 challenged the conventional description of viruses in a radical way, and since then, dozens of additional giant viruses have been identified. It has now been demonstrated that the Mimivirus genome encodes for the two enzymes required for the production of the unusual sugar 4-amino-4,6-dideoxy-d-glucose, namely a 4,6-dehydratase and an aminotransferase

    更新日期:2020-03-04
  • Introduction.
    Protein Sci. (IF 3.876) Pub Date : 2020-03-01

    更新日期:2020-03-01
  • Nucleocytoplasmic transport of intrinsically disordered proteins studied by high-speed super-resolution microscopy.
    Protein Sci. (IF 3.876) Pub Date : 2020-02-24
    Samuel L Junod,Joseph M Kelich,Jiong Ma,Weidong Yang

    Both natively folded and intrinsically disordered proteins (IDPs) destined for the nucleus need to transport through the nuclear pore complexes (NPCs) in eukaryotic cells. NPCs allow for passive diffusion of small folded proteins while barricading large ones, unless they are facilitated by nuclear transport receptors. However, whether nucleocytoplasmic transport of IDPs would follow these rules remains

    更新日期:2020-02-24
  • Structural basis of light-harvesting in the photosystem II core complex.
    Protein Sci. (IF 3.876) Pub Date : 2020-02-24
    Frank Müh,Athina Zouni

    Photosystem II (PSII) is a membrane-spanning, multi-subunit pigment-protein complex responsible for the oxidation of water and the reduction of plastoquinone in oxygenic photosynthesis. In the present review, the recent explosive increase in available structural information about the PSII core complex based on X-ray crystallography and cryo-electron microscopy is described at a level of detail that

    更新日期:2020-02-24
  • Re-examining how Munc13-1 facilitates opening of syntaxin-1.
    Protein Sci. (IF 3.876) Pub Date : 2020-02-22
    Magdalena Magdziarek,Agnieszka A Bolembach,Karolina P Stepien,Bradley Quade,Xiaoxia Liu,Josep Rizo

    Munc13-1 is crucial for neurotransmitter release and, together with Munc18-1, orchestrates assembly of the neuronal SNARE complex formed by syntaxin-1, SNAP-25 and synaptobrevin. Assembly starts with syntaxin-1 folded into a self-inhibited closed conformation that binds to Munc18-1. Munc13-1 is believed to catalyze opening of syntaxin-1 to facilitate SNARE complex formation. However, different types

    更新日期:2020-02-22
  • Insights into allosteric control of microtubule dynamics from a buried β-tubulin mutation that causes faster growth and slower shrinkage.
    Protein Sci. (IF 3.876) Pub Date : 2020-02-19
    Xuecheng Ye,Tae Kim,Elisabeth A Geyer,Luke M Rice

    αβ-tubulin subunits cycle through a series of different conformations in the polymer lattice during microtubule growing and shrinking. How these allosteric responses to different tubulin:tubulin contacts contribute to microtubule dynamics, and whether the contributions are evolutionarily conserved, remains poorly understood. Here, we sought to determine whether the microtubule-stabilizing effects (slower

    更新日期:2020-02-19
  • Bacterial secretins: Mechanisms of assembly and membrane targeting.
    Protein Sci. (IF 3.876) Pub Date : 2020-02-19
    Yuri Rafael de Oliveira Silva,Carlos Contreras-Martel,Pauline Macheboeuf,Andréa Dessen

    Secretion systems are employed by bacteria to transport macromolecules across membranes without compromising their integrities. Processes including virulence, colonization, and motility are highly dependent on the secretion of effector molecules toward the immediate cellular environment, and in some cases, into the host cytoplasm. In Type II and Type III secretion systems, as well as in Type IV pili

    更新日期:2020-02-19
  • Structure, function, and biosynthesis of nickel-dependent enzymes.
    Protein Sci. (IF 3.876) Pub Date : 2020-02-18
    Marila Alfano,Christine Cavazza

    Nickel enzymes, present in archaea, bacteria, plants, and primitive eukaryotes are divided into redox and nonredox enzymes and play key functions in diverse metabolic processes, such as energy metabolism and virulence. They catalyze various reactions by using active sites of diverse complexities, such as mononuclear nickel in Ni-superoxide dismutase, glyoxylase I and acireductone dioxygenase, dinuclear

    更新日期:2020-02-18
  • Constructing and deconstructing the bacterial cell wall.
    Protein Sci. (IF 3.876) Pub Date : 2019-11-20
    Jed F Fisher,Shahriar Mobashery

    The history of modern medicine cannot be written apart from the history of the antibiotics. Antibiotics are cytotoxic secondary metabolites that are isolated from Nature. The antibacterial antibiotics disproportionately target bacterial protein structure that is distinct from eukaryotic protein structure, notably within the ribosome and within the pathways for bacterial cell-wall biosynthesis (for

    更新日期:2020-02-14
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