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  • Solution structures of the Shewanella woodyi H‐NOX protein in the presence and absence of soluble guanylyl cyclase stimulator IWP‐051
    Protein Sci. (IF 3.876) Pub Date : 2020-11-25
    Cheng‐Yu Chen; Woonghee Lee; Paul A. Renhowe; Joon Jung; William R. Montfort

    Heme‐nitric oxide/oxygen binding (H‐NOX) domains bind gaseous ligands for signal transduction in organisms spanning prokaryotic and eukaryotic kingdoms. In the bioluminescent marine bacterium Shewanella woodyi (Sw), H‐NOX proteins regulate quorum sensing and biofilm formation. In higher animals, soluble guanylyl cyclase (sGC) binds nitric oxide with an H‐NOX domain to induce cyclase activity and regulate

  • Structural insights into a C2 domain protein specifically found in tardigrades
    Protein Sci. (IF 3.876) Pub Date : 2020-11-23
    Yohta Fukuda; Tsuyoshi Inoue

    Some tardigrades can survive extremely desiccated conditions through transition into a state called anhydrobiosis. Anhydrobiotic tardigrades have proteins unique to them and they are thought to be keys to the understanding of unusual desiccation resistance. In fact, previous transcriptome data show that several tardigrade‐specific proteins are significantly upregulated under desiccated conditions.

  • The BioGRID database: A comprehensive biomedical resource of curated protein, genetic, and chemical interactions
    Protein Sci. (IF 3.876) Pub Date : 2020-10-18
    Rose Oughtred; Jennifer Rust; Christie Chang; Bobby‐Joe Breitkreutz; Chris Stark; Andrew Willems; Lorrie Boucher; Genie Leung; Nadine Kolas; Frederick Zhang; Sonam Dolma; Jasmin Coulombe‐Huntington; Andrew Chatr‐aryamontri; Kara Dolinski; Mike Tyers

    The BioGRID (Biological General Repository for Interaction Datasets, thebiogrid.org) is an open‐access database resource that houses manually curated protein and genetic interactions from multiple species including yeast, worm, fly, mouse, and human. The ~1.93 million curated interactions in BioGRID can be used to build complex networks to facilitate biomedical discoveries, particularly as related

  • Frontotemporal dementia‐linked P112H mutation of TDP‐43 induces protein structural change and impairs its RNA binding function
    Protein Sci. (IF 3.876) Pub Date : 2020-11-05
    Sashank Agrawal; Monika Jain; Wei‐Zen Yang; Hanna S. Yuan

    TDP‐43 forms the primary constituents of the cytoplasmic inclusions contributing to various neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia (FTD). Over 60 TDP‐43 mutations have been identified in patients suffering from these two diseases, but most variations are located in the protein's disordered C‐terminal glycine‐rich region. P112H mutation of TDP‐43

  • In‐depth interrogation of protein thermal unfolding data with MoltenProt
    Protein Sci. (IF 3.876) Pub Date : 2020-11-02
    Vadim Kotov; Georg Mlynek; Oliver Vesper; Marina Pletzer; Jiri Wald; Celso M. Teixeira‐Duarte; Herve Celia; Maria Garcia‐Alai; Stephan Nussberger; Susan K. Buchanan; João H. Morais‐Cabral; Christian Loew; Kristina Djinovic‐Carugo; Thomas C. Marlovits

    Protein stability is a key factor in successful structural and biochemical research. However, the approaches for systematic comparison of protein stability are limited by sample consumption or compatibility with sample buffer components. Here we describe how miniaturized measurement of intrinsic tryptophan fluorescence (NanoDSF assay) in combination with a simplified description of protein unfolding

  • In This Issue
    Protein Sci. (IF 3.876) Pub Date : 2020-11-21

    2433 Computational design of mixed chirality peptide macrocycles with internal symmetry Vikram Khipple Mulligan, Christine S. Kang, Michael R. Sawaya, Stephen Rettie, Xinting Li, Inna Antselovich, Timothy W. Craven, Andrew M. Watkins, Jason W. Labonte, Frank DiMaio, Todd O. Yeates, David Baker Peptides synthesized from non‐canonical amino acids can adopt exotic folds inaccessible to natural proteins

  • Biosynthesis of depsipeptides, or Depsi: The peptides with varied generations
    Protein Sci. (IF 3.876) Pub Date : 2020-10-19
    Diego A. Alonzo; T. Martin Schmeing

    Depsipeptides are compounds that contain both ester bonds and amide bonds. Important natural product depsipeptides include the piscicide antimycin, the K+ ionophores cereulide and valinomycin, the anticancer agent cryptophycin, and the antimicrobial kutzneride. Furthermore, database searches return hundreds of uncharacterized systems likely to produce novel depsipeptides. These compounds are made by

  • How bilayer properties influence membrane protein folding
    Protein Sci. (IF 3.876) Pub Date : 2020-10-15
    Karolina Corin; James U. Bowie

    The question of how proteins manage to organize into a unique three‐dimensional structure has been a major field of study since the first protein structures were determined. For membrane proteins, the question is made more complex because, unlike water‐soluble proteins, the solvent is not homogenous or even unique. Each cell and organelle has a distinct lipid composition that can change in response

  • Cryo‐electron microscopy structure of human ABCB6 transporter
    Protein Sci. (IF 3.876) Pub Date : 2020-10-02
    Chunyu Wang; Can Cao; Nan Wang; Xiangxi Wang; Xianping Wang; Xuejun C. Zhang

    Human ATP‐binding cassette transporter 6 of subfamily B (ABCB6) is an ABC transporter involved in the translocation toxic metals and anti‐cancer drugs. Using cryo‐electron microscopy, we determined the molecular structure of full‐length ABCB6 in an apo state. The structure of ABCB6 unravels the architecture of a full‐length ABCB transporter that harbors two N‐terminal transmembrane domains which is

  • Influence of circular permutations on the structure and stability of a six‐fold circular symmetric designer protein
    Protein Sci. (IF 3.876) Pub Date : 2020-10-02
    Bram Mylemans; Hiroki Noguchi; Els Deridder; Eveline Lescrinier; Jeremy R. H. Tame; Arnout R. D. Voet

    The β‐propeller fold is adopted by a sequentially diverse family of repeat proteins with apparent rotational symmetry. While the structure is mostly stabilized by hydrophobic interactions, an additional stabilization is provided by hydrogen bonds between the N‐and C‐termini, which are almost invariably part of the same β‐sheet. This feature is often referred to as the “Velcro” closure. The positioning

  • Kinetic characterization and structure analysis of an altered polyol dehydrogenase with d‐lactate dehydrogenase activity
    Protein Sci. (IF 3.876) Pub Date : 2020-10-05
    Diane Chauliac; Qingzhao Wang; Franz J. St. John; Grace Jones; Jason C. Hurlbert; Lonnie O. Ingram; Keelnatham T. Shanmugam

    During adaptive metabolic evolution a native glycerol dehydrogenase (GDH) acquired a d‐lactate dehydrogenase (LDH) activity. Two active‐site amino acid changes were detected in the altered protein. Biochemical studies along with comparative structure analysis using an X‐ray crystallographic structure model of the protein with the two different amino acids allowed prediction of pyruvate binding into

  • Consensus mutagenesis approach improves the thermal stability of system xc− transporter, xCT, and enables cryo‐EM analyses
    Protein Sci. (IF 3.876) Pub Date : 2020-10-05
    Kazumasa Oda; Yongchan Lee; Pattama Wiriyasermkul; Yoko Tanaka; Mizuki Takemoto; Keitaro Yamashita; Shushi Nagamori; Tomohiro Nishizawa; Osamu Nureki

    System xc− is an amino acid antiporter that imports L‐cystine into cells and exports intracellular L‐glutamate, at a 1:1 ratio. As L‐cystine is an essential precursor for glutathione synthesis, system xc− supports tumor cell growth through glutathione‐based oxidative stress resistance and is considered as a potential therapeutic target for cancer treatment. System xc− consists of two subunits, the

  • A kinetic coupling between protein unfolding and aggregation controls time‐dependent solubility of the human myeloma antibody light chain
    Protein Sci. (IF 3.876) Pub Date : 2020-10-08
    Veronika Džupponová; Veronika Huntošová; Gabriel Žoldák

    Protein aggregation is one of the most critical processes affecting protein solubility in various contexts—from protein therapeutics formulation to protein diseases. In general, time‐dependent changes in protein solubility are complex kinetically driven processes that often involve a triggering event that consists of a protein unfolding/misfolding followed by the assembling of aggregation‐competent

  • Molecular basis of the interaction of Hsp90 with its co‐chaperone Hop
    Protein Sci. (IF 3.876) Pub Date : 2020-10-11
    Antonia Lott; Javier Oroz; Markus Zweckstetter

    The heat shock protein (Hsp) Hsp90 is one of the most abundant proteins in the cell. It controls the functional turnover of proteins being involved in protein folding, refolding, transport as well as protein degradation. Co‐chaperones influence Hsp90's activity in different ways, among which the Hsp organizing protein (Hop) was found to inhibit its ATP hydrolysis upon binding. Despite the availability

  • Computational design of mixed chirality peptide macrocycles with internal symmetry
    Protein Sci. (IF 3.876) Pub Date : 2020-10-15
    Vikram Khipple Mulligan; Christine S. Kang; Michael R. Sawaya; Stephen Rettie; Xinting Li; Inna Antselovich; Timothy W. Craven; Andrew M. Watkins; Jason W. Labonte; Frank DiMaio; Todd O. Yeates; David Baker

    Cyclic symmetry is frequent in protein and peptide homo‐oligomers, but extremely rare within a single chain, as it is not compatible with free N‐ and C‐termini. Here we describe the computational design of mixed‐chirality peptide macrocycles with rigid structures that feature internal cyclic symmetries or improper rotational symmetries inaccessible to natural proteins. Crystal structures of three C2‐

  • Chlamydia trachomatis glyceraldehyde 3‐phosphate dehydrogenase: Enzyme kinetics, high‐resolution crystal structure, and plasminogen binding
    Protein Sci. (IF 3.876) Pub Date : 2020-10-15
    Norbert Schormann; Juan Campos; Rachael Motamed; Katherine L. Hayden; Joseph R. Gould; Todd J. Green; Olga Senkovich; Surajit Banerjee; Glen C. Ulett; Debasish Chattopadhyay

    Glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) is an evolutionarily conserved essential enzyme in the glycolytic pathway. GAPDH is also involved in a wide spectrum of non‐catalytic cellular ‘moonlighting’ functions. Bacterial surface‐associated GAPDHs engage in many host interactions that aid in colonization, pathogenesis, and virulence. We have structurally and functionally characterized the recombinant

  • Hydrogels from serum albumin in a molten globule‐like state
    Protein Sci. (IF 3.876) Pub Date : 2020-10-15
    Seyed Hamidreza Arabi; Behdad Aghelnejad; Jonas Volmer; Dariush Hinderberger

    We demonstrate that a molten globule‐like (MG) state of a protein, usually described as a compact yet non‐folded conformation that is only present in a narrow and delicate parameter range, is preserved in the high concentration environment of the protein hydrogel. We reveal mainly by means of electron paramagnetic resonance (EPR) spectroscopy that bovine serum albumin (BSA) retains the known basic

  • Crystal structure of the giant panda MHC class I complex: First insights into the viral peptide presentation profile in the bear family
    Protein Sci. (IF 3.876) Pub Date : 2020-10-20
    Hongyu Yuan; Lizhen Ma; Lijie Zhang; Xiaoying Li; Chun Xia

    The viral cytotoxic T lymphocyte (CTL) epitope peptides presented by classical MHC‐I molecules require the assembly of a peptide‐MHC‐I‐β2m (pMHC‐I) trimolecular complex for T cell receptor (TCR) recognition, which is the critical activation link for triggering antiviral T cell immunity. Research on T cell immunology in the Ursidae family, especially structural immunology, is still lacking. In this

  • Ligand binding and global adaptation of the GlnPQ substrate binding domain 2 revealed by molecular dynamics simulations
    Protein Sci. (IF 3.876) Pub Date : 2020-10-18
    Maximilian Kienlein; Martin Zacharias

    Substrate‐binding domains (SBD) are important structural elements of substrate transporters mediating the transport of essential molecules across the cell membrane. The SBD2 domain of the glutamine (GLN) transporter from bacteria consists of two domains D1 and D2 that bind GLN in the space between the domains in a closed conformation. In the absence of ligand, SBD2 adopts an open conformation with

  • Pyrexia and acidosis act independently of neutrophil elastase reactive center loop cleavage to effect cortisol release from corticosteroid‐binding globulin
    Protein Sci. (IF 3.876) Pub Date : 2020-10-21
    Emily J. Meyer; David J. Torpy; Anastasia Chernykh; Morten Thaysen‐Andersen; Marni A. Nenke; John G. Lewis; Harinda Rajapaksha; Wayne Rankin; Steven W. Polyak

    Corticosteroid‐binding globulin (CBG) transports cortisol and other steroids. High‐affinity CBG (haCBG) undergoes proteolysis of the reactive center loop (RCL) by neutrophil elastase (NE) altering conformation to low‐affinity CBG (laCBG). Elevated temperature reduces CBG:cortisol binding affinity. Surface plasmon resonance was used to determine binding profiles of 19 steroids to haCBG and laCBG at

  • Molecular and structural analysis of central transport channel in complex with Nup93 of nuclear pore complex
    Protein Sci. (IF 3.876) Pub Date : 2020-10-21
    Parshuram J. Sonawane; Pravin S. Dewangan; Pankaj Kumar Madheshiya; Kriti Chopra; Mohit Kumar; Sangeeta Niranjan; Mohammed Yousuf Ansari; Jyotsana Singh; Shrankhla Bawaria; Manidipa Banerjee; Radha Chauhan

    The central transport channel (CTC) of nuclear pore complexes (NPCs) is made up of three nucleoporins Nup62, Nup58 and Nup54. In which manner and capacity, these nucleoporins form the CTC, is not yet clear. We explored the CTC Nups from various species and observed that distinct biochemical characteristics of CTC Nups are evolutionarily conserved. Moreover, comparative biochemical analysis of CTC complexes

  • The pMy vector series: A versatile cloning platform for the recombinant production of mycobacterial proteins in Mycobacterium smegmatis
    Protein Sci. (IF 3.876) Pub Date : 2020-10-02
    Katherine S. H. Beckham; Sonja Staack; Matthias Wilmanns; Annabel H. A. Parret

    Structural and biophysical characterization of molecular mechanisms of disease‐causing pathogens, such as Mycobacterium tuberculosis, often requires recombinant expression of large amounts highly pure protein. For the production of mycobacterial proteins, overexpression in the fast‐growing and non‐pathogenic species Mycobacterium smegmatis has several benefits over the standard Escherichia coli expression

  • Structural basis for thioredoxin isoform‐based fine‐tuning of ferredoxin‐thioredoxin reductase activity
    Protein Sci. (IF 3.876) Pub Date : 2020-10-04
    Linda Juniar; Hideaki Tanaka; Keisuke Yoshida; Toru Hisabori; Genji Kurisu

    Photosynthetic electron transport occurs on the thylakoid membrane of chloroplasts. Ferredoxin (Fd), the final acceptor in the electron transport chain, distributes electrons to several Fd‐dependent enzymes including Fd‐thioredoxin reductase (FTR). A cascade from Fd to FTR further reduces Thioredoxin (Trx), which tunes the activity of target metabolic enzymes eventually in a light‐dependent manner

  • The ImageJ ecosystem: Open‐source software for image visualization, processing, and analysis
    Protein Sci. (IF 3.876) Pub Date : 2020-11-09
    Alexandra B. Schroeder; Ellen T. A. Dobson; Curtis T. Rueden; Pavel Tomancak; Florian Jug; Kevin W. Eliceiri

    For decades, biologists have relied on software to visualize and interpret imaging data. As techniques for acquiring images increase in complexity, resulting in larger multidimensional datasets, imaging software must adapt. ImageJ is an open‐source image analysis software platform that has aided researchers with a variety of image analysis applications, driven mainly by engaged and collaborative user

  • Study of the TEAD‐binding domain of the YAP protein from animal species
    Protein Sci. (IF 3.876) Pub Date : 2020-11-04
    Yannick Mesrouze; Fedir Bokhovchuk; Marco Meyerhofer; Catherine Zimmermann; Patrizia Fontana; Dirk Erdmann; Patrick Chène

    The Hippo signaling pathway, which plays a central role in the control of organ size in animals, is well conserved in metazoans. The most downstream elements of this pathway are the TEAD transcription factors that are regulated by their association with the transcriptional coactivator YAP. Therefore, the creation of the binding interface that ensures the formation of the YAP:TEAD complex is a critical

  • Structural motifs in protein cores and at protein–protein interfaces are different
    Protein Sci. (IF 3.876) Pub Date : 2020-11-09
    Anna Hadarovich; Devlina Chakravarty; Alexander V. Tuzikov; Nir Ben‐Tal; Petras J. Kundrotas; Ilya A. Vakser

    Structures of proteins and protein–protein complexes are determined by the same physical principles and thus share a number of similarities. At the same time, there could be differences because in order to function, proteins interact with other molecules, undergo conformations changes, and so forth, which might impose different restraints on the tertiary versus quaternary structures. This study focuses

  • Tracking exogenous intracellular casp‐3 using split GFP
    Protein Sci. (IF 3.876) Pub Date : 2020-11-09
    Francesca Anson; Pintu Kanjilal; S. Thayumanavan; Jeanne A. Hardy

    Cytosolic protein delivery promises diverse applications from therapeutics, to genetic modification and precision research tools. To achieve effective cellular and subcellular delivery, approaches that allow protein visualization and accurate localization with greater sensitivity are essential. Fluorescently tagging proteins allows detection, tracking and visualization in cellulo. However, undesired

  • Structural insights into the tropomodulin assembly at the pointed ends of actin filaments
    Protein Sci. (IF 3.876) Pub Date : 2020-11-18
    Dmitri Tolkatchev; Balaganesh Kuruba; Garry E. Smith; Kyle D. Swain; Kaitlin A. Smith; Natalia Moroz; Trenton J. Williams; Alla S. Kostyukova

    Tropomodulins are a family of important regulators of actin dynamics at the pointed ends of actin filaments. Four isoforms of tropomodulin, Tmod1‐Tmod4, are expressed in vertebrates. Binding of tropomodulin to the pointed end is dependent on tropomyosin, an actin binding protein that itself is represented in mammals by up to 40 isoforms. The understanding of the regulatory role of the tropomodulin/tropomyosin

  • qFit 3: Protein and ligand multiconformer modeling for X‐ray crystallographic and single‐particle cryo‐EM density maps
    Protein Sci. (IF 3.876) Pub Date : 2020-11-18
    Blake T. Riley; Stephanie A. Wankowicz; Saulo H. P. de Oliveira; Gydo C. P. van Zundert; Daniel W. Hogan; James S. Fraser; Daniel A. Keedy; Henry van den Bedem

    New X‐ray crystallography and cryo‐electron microscopy (cryo‐EM) approaches yield vast amounts of structural data from dynamic proteins and their complexes. Modeling the full conformational ensemble can provide important biological insights, but identifying and modeling an internally consistent set of alternate conformations remains a formidable challenge. qFit efficiently automates this process by

  • TSGIT: An N‐ and C‐terminal tandem tag system for purification of native and intein‐mediated ligation‐ready proteins
    Protein Sci. (IF 3.876) Pub Date : 2020-11-05
    Vlad‐Stefan Raducanu; Daniela‐Violeta Raducanu; Yujing Ouyang; Muhammad Tehseen; Masateru Takahashi; Samir M. Hamdan

    A large variety of fusion tags have been developed to improve protein expression, solubilization, and purification. Nevertheless, these tags have been combined in a rather limited number of composite tags and usually these composite tags have been dictated by traditional commercially‐available expression vectors. Moreover, most commercially‐available expression vectors include either N‐ or C‐terminal

  • Nanodiscs: A toolkit for membrane protein science
    Protein Sci. (IF 3.876) Pub Date : 2020-11-09
    Stephen G. Sligar; Ilia G. Denisov

    Membrane proteins are involved in numerous vital biological processes, including transport, signal transduction and the enzymes in a variety of metabolic pathways. Integral membrane proteins account for up to 30% of the human proteome and they make up more than half of all currently marketed therapeutic targets. Unfortunately, membrane proteins are inherently recalcitrant to study using the normal

  • Structural insight into the novel iron‐coordination and domain interactions of transferrin‐1 from a model insect, Manduca sexta
    Protein Sci. (IF 3.876) Pub Date : 2020-11-16
    Jacob J. Weber; Maithri M. Kashipathy; Kevin P. Battaile; Eden Go; Heather Desaire; Michael R. Kanost; Scott Lovell; Maureen J. Gorman

    Transferrins function in iron sequestration and iron transport by binding iron tightly and reversibly. Vertebrate transferrins coordinate iron through interactions with two tyrosines, an aspartate, a histidine, and a carbonate anion, and conformational changes that occur upon iron binding and release have been described. Much less is known about the structure and functions of insect transferrin‐1 (Tsf1)

  • Conserved patterns and interactions in the unfolding transition state across SH3 domain structural homologues
    Protein Sci. (IF 3.876) Pub Date : 2020-11-14
    Cullen Demakis; Matthew C. Childers; Valerie Daggett

    Proteins with similar structures are generally assumed to arise from similar sequences. However, there are more cases than not where this is not true. The dogma is that sequence determines structure; how, then, can very different sequences fold to the same structure? Here, we employ high temperature unfolding simulations to probe the pathways and specific interactions that direct the folding and unfolding

  • The Human Protein Atlas—Spatial localization of the human proteome in health and disease
    Protein Sci. (IF 3.876) Pub Date : 2020-11-04
    Andreas Digre; Cecilia Lindskog

    For a complete understanding of a system's processes and each protein's role in health and disease, it is essential to study protein expression with a spatial resolution, as the exact location of proteins at tissue, cellular, or subcellular levels is tightly linked to protein function. The Human Protein Atlas (HPA) project is a large‐scale initiative aiming at mapping the entire human proteome using

  • Templates for Writing PyMOL Scripts
    Protein Sci. (IF 3.876) Pub Date : 2020-11-11
    Blaine H. M. Mooers; Marina Brown

    PyMOL commands are used to exert exquisite control over the appearance of a molecular model. This control has made PyMOL popular for making images of protein structures for publications and presentations. However, many users have poor recall of the commands due to infrequent use of PyMOL. This poor recall hinders the writing of new code in scripts. One solution is to build the new script by using code

  • Ethanol‐soluble proteins from the royal jelly of Xinjiang black bees
    Protein Sci. (IF 3.876) Pub Date : 2020-11-01
    Yanyan Yuan; Wujun Wang; Ruru Fan; Jianhui Jiang; Shan Feng; Huiwei Yin; Shi‐Zhong Luo; Long Chen

    Royal jelly is a nutritious food that has beneficial effects to human health. However, the functional substances remain unclear. Herein, we fractioned the royal jelly proteins of Xinjing black bees according to the Osboren method. Two main proteins from the ethanol‐soluble fraction were purified and identified. RJG‐1 was determined as glucosylceramidase, and RJG‐2 was major royal jelly protein 1 (MRJP1)

  • Using Integrative Modeling Platform to Compute, Validate, and Archive a Model of a Protein Complex Structure
    Protein Sci. (IF 3.876) Pub Date : 2020-11-09
    Daniel J. Saltzberg; Shruthi Viswanath; Ignacia Echeverria; Ilan E. Chemmama; Ben Webb; Andrej Sali

    Biology is advanced by producing structural models of biological systems, such as protein complexes. Some systems are recalcitrant to traditional structure determination methods. In such cases, it may still be possible to produce useful models by integrative structure determination that depends on simultaneous use of multiple types of data. An ensemble of models that are sufficiently consistent with

  • A collection of programs for one‐dimensional Ising analysis of linear repeat proteins with point substitutions
    Protein Sci. (IF 3.876) Pub Date : 2020-10-15
    Jacob D. Marold; Kevin Sforza; Kathryn Geiger‐Schuller; Tural Aksel; Sean Klein; Mark Petersen; Ekaterina Poliakova‐Georgantas; Doug Barrick

    A collection of programs is presented to analyze the thermodynamics of folding of linear repeat proteins using a 1D Ising model to determine intrinsic folding and interfacial coupling free energies. Expressions for folding transitions are generated for a series of constructs with different repeat numbers and are globally fitted to transitions for these constructs. These programs are designed to analyze

  • SynPharm and the guide to pharmacology database: A toolset for conferring drug control on engineered proteins
    Protein Sci. (IF 3.876) Pub Date : 2020-10-12
    Jamie A. Davies

    Optimizing synthetic biological systems, for example novel metabolic pathways, becomes more complicated with more protein components. One method of taming the complexity and allowing more rapid optimization is engineering external control into components. Pharmacology is essentially the science of controlling proteins using (mainly) small molecules, and a great deal of information, spread between different

  • Reaction mechanism of tetrathionate hydrolysis based on the crystal structure of tetrathionate hydrolase from Acidithiobacillus ferrooxidans
    Protein Sci. (IF 3.876) Pub Date : 2020-10-25
    Tadayoshi Kanao; Naruki Hase; Hisayuki Nakayama; Kyoya Yoshida; Kazumi Nishiura; Megumi Kosaka; Kazuo Kamimura; Yu Hirano; Taro Tamada

    Tetrathionate hydrolase (4THase) plays an important role in dissimilatory sulfur oxidation in the acidophilic iron‐ and sulfur‐oxidizing bacterium Acidithiobacillus ferrooxidans. The structure of recombinant 4THase from A. ferrooxidans (Af‐Tth) was determined by X‐ray crystallography to a resolution of 1.95 å. Af‐Tth is a homodimer, and its monomer structure exhibits an eight‐bladed β‐propeller motif

  • The AbDesign computational pipeline for modular backbone assembly and design of binders and enzymes
    Protein Sci. (IF 3.876) Pub Date : 2020-10-11
    Rosalie Lipsh‐Sokolik; Dina Listov; Sarel J. Fleishman

    The functional sites of many protein families are dominated by diverse backbone regions that lack secondary structure (loops) but fold stably into their functionally competent state. Nevertheless, the design of structured loop regions from scratch, especially in functional sites, has met with great difficulty. We therefore developed an approach, called AbDesign, to exploit the natural modularity of

  • In This Issue
    Protein Sci. (IF 3.876) Pub Date : 2020-10-26

    2164 The high‐resolution structure of a UDP‐L‐rhamnose synthase from Acanthamoeba polyphaga Mimivirus Nicholas J. Bockhaus, Justin D. Ferek, James B. Thoden, Hazel M. Holden A simple perusal of the literature shows the importance of viral research in elucidating such fundamental processes as DNA replication. Indeed, given the current deadly pandemic resulting from the coronavirus, SARS‐CoV‐2, it is

  • PAINT using proteins: A new brush for super-resolution artists.
    Protein Sci. (IF 3.876) Pub Date : 2020-09-18
    Curran Oi,Simon Mochrie,Mathew Horrocks,Lynne Regan

    PAINT (points accumulation for imaging in nanoscale topography) refers to methods that achieve the sparse temporal labeling required for super‐resolution imaging by using transient interactions between a biomolecule of interest and a fluorophore. There have been a variety of different implementations of this method since it was first described in 2006. Recent papers illustrate how transient peptide–protein

  • Substitution Scoring Matrices for Proteins - An Overview.
    Protein Sci. (IF 3.876) Pub Date : 2020-09-21
    Rakesh Trivedi,Hampapathalu Adimurthy Nagarajaram

    Sequence analysis is the primary and simplest approach to discover structural, functional and evolutionary details of related proteins. All the alignment based approaches of sequence analysis make use of amino acid substitution matrices, and the accuracy of the results largely depends on the type of scoring matrices used to perform alignment tasks. An amino acid substitution matrix is a 20 × 20 matrix

  • Development and characterization of specific anti-Usutu virus chicken-derived single chain variable fragment antibodies.
    Protein Sci. (IF 3.876) Pub Date : 2020-08-23
    Amelie Karin Josephine Schoenenwald,Chin Piaw Gwee,Karin Stiasny,Marcela Hermann,Subhash G Vasudevan,Tim Skern

    Usutu virus belongs to the Japanese encephalitis serogroup within the Flaviviridae family. Mammals may become incidental hosts after the bite of an infected mosquito while birds act as the main reservoir. Human cases have become more common recently and elicit various outcomes ranging from asymptomatic to severe illness including encephalitis. Problematically, antisera against Usutu virus cross‐react

  • Metabolites modulate the functional state of human uridine phosphorylase I.
    Protein Sci. (IF 3.876) Pub Date : 2020-08-30
    Yu-Ting Huang,Pei-Chin Yeh,Shih-Chun Lan,Pei-Fen Liu

    Metabolic pathways in cancer cells typically become reprogrammed to support unconstrained proliferation. These abnormal metabolic states are often accompanied by accumulation of high concentrations of ATP in the cytosol, a phenomenon known as the Warburg Effect. However, how high concentrations of ATP relate to the functional state of proteins is poorly understood. Here, we comprehensively studied

  • Symmetry breaking and structural polymorphism in a bacterial microcompartment shell protein for choline utilization.
    Protein Sci. (IF 3.876) Pub Date : 2020-09-04
    Jessica M Ochoa,Vy N Nguyen,Mengxiao Nie,Michael R Sawaya,Thomas A Bobik,Todd O Yeates

    Bacterial microcompartments are protein‐based organelles that carry out specialized metabolic functions in diverse bacteria. Their outer shells are built from several thousand protein subunits. Some of the architectural principles of bacterial microcompartments have been articulated, with lateral packing of flat hexameric BMC proteins providing the basic foundation for assembly. Nonetheless, a complete

  • Structural basis of strict substrate recognition of l-lysine α-oxidase from Trichoderma viride.
    Protein Sci. (IF 3.876) Pub Date : 2020-09-07
    Hiroki Kondo,Masaki Kitagawa,Yuya Matsumoto,Masaya Saito,Marie Amano,Shigeru Sugiyama,Takashi Tamura,Hitoshi Kusakabe,Kenji Inagaki,Katsumi Imada

    l‐Lysine oxidase (LysOX) is a FAD‐dependent homodimeric enzyme that catalyzes the oxidative deamination of l‐lysine to produce α‐keto‐ε‐aminocaproate with ammonia and hydrogen peroxide. LysOX shows strict substrate specificity for l‐lysine, whereas most l‐amino acid oxidases (LAAOs) exhibit broad substrate specificity for l‐amino acids. Previous studies of LysOX showed that overall structural similarity

  • Structural Characterization and Computational Analysis of PDZ domains in Monosiga brevicollis.
    Protein Sci. (IF 3.876) Pub Date : 2020-09-10
    Melody Gao,Iain G P Mackley,Samaneh Mesbahi-Vasey,Haley A Bamonte,Sarah A Struyvenberg,Louisa Landolt,Nick J Pederson,Lucy I Williams,Christopher D Bahl,Lionel Brooks,Jeanine F Amacher

    Identification of the molecular networks that facilitated the evolution of multicellular animals from their unicellular ancestors is a fundamental problem in evolutionary cellular biology. Choanoflagellates are recognized as the closest extant nonmetazoan ancestors to animals. These unicellular eukaryotes can adopt a multicellular‐like “rosette” state. Therefore, they are compelling models for the

  • Structure of the Plasmodium falciparum PfSERA5 pseudo-zymogen.
    Protein Sci. (IF 3.876) Pub Date : 2020-09-21
    Nicholas A Smith,Oliver B Clarke,Mihwa Lee,Anthony N Hodder,Brian J Smith

    PfSERA5, a significantly abundant protein present within the parasitophorous vacuole (PV) and essential for normal growth during the blood‐stage life cycle of the malaria parasite Plasmodium falciparum, displays structural similarity to many other cysteine proteases. However, PfSERA5 does not exhibit any detectable protease activity and therefore the role of the PfSERA5 papain‐like domain (PfSERA5E)

  • Learning peptide recognition rules for a low‐specificity protein
    Protein Sci. (IF 3.876) Pub Date : 2020-09-26
    Lucas C. Wheeler; Arden Perkins; Caitlyn E. Wong; Michael J. Harms

    Many proteins interact with short linear regions of target proteins. For some proteins, however, it is difficult to identify a well‐defined sequence motif that defines its target peptides. To overcome this difficulty, we used supervised machine learning to train a model that treats each peptide as a collection of easily‐calculated biochemical features rather than as an amino acid sequence. As a test

  • Solution NMR structure of Se0862, a highly conserved cyanobacterial protein involved in biofilm formation.
    Protein Sci. (IF 3.876) Pub Date : 2020-09-18
    Ning Zhang,Yong-Gang Chang,Roger Tseng,Sergey Ovchinnikov,Rakefet Schwarz,Andy LiWang

    Biofilms are accumulations of microorganisms embedded in extracellular matrices that protect against external factors and stressful environments. Cyanobacterial biofilms are ubiquitous and have potential for treatment of wastewater and sustainable production of biofuels. But the underlying mechanisms regulating cyanobacterial biofilm formation are unclear. Here, we report the solution NMR structure

  • Self-assembling peptides: from a discovery in a yeast protein to diverse uses and beyond.
    Protein Sci. (IF 3.876) Pub Date : 2020-09-16
    Shuguang Zhang

    Well‐defined nanofiber scaffold hydrogels made of self‐assembling peptides have found their way into various 3D tissue culture and clinical products. I reflect initial puzzlement of the unexpected discovery, gradual understanding of how these peptides undergo self‐assembly, to eventually translating designer biological scaffolds into commercial products. Peptides are ubiquitous in nature and useful

  • Roles of Variable Linker Length in Dual Acting Virucidal Entry Inhibitors on HIV-1 Potency via On-the-fly Free Energy Molecular Simulations.
    Protein Sci. (IF 3.876) Pub Date : 2020-09-14
    Steven T Gossert,Bibek Parajuli,Irwin Chaiken,Cameron F Abrams

    The Dual‐Acting Virolytic Entry Inhibitors, or DAVEI's, are a class of recombinant chimera fusion proteins consisting of a lectin, a flexible polypeptide linker, and a fragment of the membrane‐proximal external region (MPER) of HIV‐1 gp41. DAVEIs trigger virolysis of HIV‐1 virions through interactions with the trimeric envelope glycoprotein complex (Env), though the details of these interactions are

  • UCSF ChimeraX: Structure Visualization for Researchers, Educators, and Developers.
    Protein Sci. (IF 3.876) Pub Date : 2020-09-03
    Eric F Pettersen,Thomas D Goddard,Conrad C Huang,Elaine C Meng,Gregory S Couch,Tristan I Croll,John H Morris,Thomas E Ferrin

    UCSF ChimeraX is the next‐generation interactive visualization program from the Resource for Biocomputing, Visualization, and Informatics (RBVI), following UCSF Chimera. ChimeraX brings (a) significant performance and graphics enhancements; (b) new implementations of Chimera's most highly used tools, many with further improvements; (c) several entirely new analysis features; (d) support for new areas

  • Iris: interactive all-in-one graphical validation of 3D protein model iterations.
    Protein Sci. (IF 3.876) Pub Date : 2020-09-23
    William Rochira,Jon Agirre

    Iris validation is a Python package created to represent comprehensive per‐residue validation metrics for entire protein chains in a compact, readable and interactive view. These metrics can either be calculated by Iris, or by a third‐party program such as MolProbity. We show that those parts of a protein model requiring attention may generate ripples across the metrics on the diagram, immediately

  • MMM: Integrative ensemble modeling and ensemble analysis
    Protein Sci. (IF 3.876) Pub Date : 2020-10-04
    Gunnar Jeschke

    Proteins and their complexes can be heterogeneously disordered. In ensemble modeling of such systems with restraints from several experimental techniques the following problems arise: (a) integration of diverse restraints obtained on different samples under different conditions; (b) estimation of a realistic ensemble width; (c) sufficient sampling of conformational space; (d) representation of the

  • InteBac - An integrated bacterial and baculovirus expression vector suite.
    Protein Sci. (IF 3.876) Pub Date : 2020-09-21
    Veronika Altmannova,Andreas Blaha,Susanne Astrinidis,Heidi Reichle,John R Weir

    The successful production of recombinant protein for biochemical, biophysical, and structural biological studies critically depends on the correct expression organism. Currently, the most commonly used expression organisms for structural studies are Escherichia coli (~70% of all PDB structures) and the baculovirus/ insect cell expression system (~5% of all PDB structures). While insect cell expression

  • Leginon: New Features and Applications
    Protein Sci. (IF 3.876) Pub Date : 2020-10-08
    Anchi Cheng; Carl Negro; Jessica F. Bruhn; William J. Rice; Sargis Dallakyan; Edward T. Eng; David G. Waterman; Clinton S. Potter; Bridget Carragher

    Leginon is a system for automated data acquisition from a transmission electron microscope. Here we provide an updated summary of the overall Leginon architecture and an update of the current state of the package. We also highlight a few recent developments to provide some concrete examples and use cases.

  • Covid‐19.bioreproducibility.org: A web resource for SARS‐CoV‐2‐related structural models
    Protein Sci. (IF 3.876) Pub Date : 2020-09-27
    Dariusz Brzezinski; Marcin Kowiel; David R. Cooper; Marcin Cymborowski; Marek Grabowski; Alexander Wlodawer; Zbigniew Dauter; Ivan G. Shabalin; Miroslaw Gilski; Bernhard Rupp; Mariusz Jaskolski; Wladek Minor

    The COVID‐19 pandemic has triggered numerous scientific activities aimed at understanding the SARS‐CoV‐2 virus and ultimately developing treatments. Structural biologists have already determined hundreds of experimental X‐ray, cryo‐EM, and NMR structures of proteins and nucleic acids related to this coronavirus, and this number is still growing. To help biomedical researchers, who may not necessarily

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