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  • 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

  • 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

  • A phage-displayed single-chain Fab library optimized for rapid production of single-chain IgGs.
    Protein Sci. (IF 3.876) Pub Date : 2020-08-17
    Rachel Hanna,Lia Cardarelli,Nish Patel,Levi L Blazer,Jarrett J Adams,Sachdev S Sidhu

    Phage‐displayed synthetic antibody (Ab) repertoires have become a major source of affinity reagents for basic and clinical research. Specific Abs identified from such libraries are often screened as fragments antigen binding (Fabs) produced in bacteria, and those with desired biochemical characteristics are reformatted for production as full‐length immunoglobulin G (IgG) in mammalian cells. The conversion

  • 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. DAVEI's trigger virolysis of HIV‐1 virions through interactions with the trimeric envelope glycoprotein complex (Env), though the details of these interactions are

  • 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

  • Erratum
    Protein Sci. (IF 3.876) Pub Date : 2020-09-14

    Han, M., Liao, S., Peng, X., Zhou, X., Chen, Q. and Liu, H. (2019), Selection and analyses of variants of a designed protein suggest importance of hydrophobicity of partially buried sidechains for protein stability at high temperatures. Protein Science, 28:1437–1,447. doi:10.1002/pro.3643 In the originally published version, author Shanhui Liao’s name was spelled incorrectly. The correct name appears

    Protein Sci. (IF 3.876) Pub Date : 2020-09-14

    Corrigendum to “Three‐dimensional organization of the cytoskeleton: A cryo‐electron tomography perspective” Saikat Chakraborty, Marion Jasnin and Wolfgang Baumeister Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany (Linked DOI: 10.1002/pro.3858) After the publication of our review article, we noticed that we missed a few

  • How to use the MEROPS database and website to help understand peptidase specificity
    Protein Sci. (IF 3.876) Pub Date : 2020-09-13
    Neil D. Rawlings; Alex Bateman

    The MEROPS website (https://www.ebi.ac.uk/merops) and database was established in 1996 to present the classification and nomenclature of proteolytic enzymes. This was expanded to include a classification of protein inhibitors of proteolytic enzymes in 2004. Each peptidase or inhibitor is assigned to a distinct identifier, based on its biochemical and biological properties, and homologous sequences

  • The AutoDock Suite at 30.
    Protein Sci. (IF 3.876) Pub Date : 2020-08-17
    David S Goodsell,Michel Sanner,Arthur J Olson,Stefano Forli

    The AutoDock suite provides a comprehensive toolset for computational ligand docking and drug design and development. The suite builds on 30 years of methods development, including empirical free energy force fields, docking engines, methods for site prediction, and interactive tools for visualization and analysis. Specialized tools are available for challenging systems, including covalent inhibitors

  • 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 non‐metazoan ancestors to animals. These unicellular eukaryotes can adopt a multicellular‐like “rosette” state. Therefore, they are compelling models for the

  • DynaMut2: Assessing changes in stability and flexibility upon single and multiple point missense mutations.
    Protein Sci. (IF 3.876) Pub Date : 2020-09-03
    Carlos H M Rodrigues,Douglas E V Pires,David B Ascher

    Predicting the effect of missense variations on protein stability and dynamics is important for understanding their role in diseases, and the link between protein structure and function. Approaches to estimate these changes have been proposed, but most only consider single‐point missense variants and a static state of the protein, with those that incorporate dynamics are computationally expensive.

  • High resolution electron tomography and segmentation‐by‐modeling interpretation in Bsoft
    Protein Sci. (IF 3.876) Pub Date : 2020-08-27
    J. Bernard Heymann

    Bsoft offers many tools for the processing of tomographic tilt series and the interpretation of tomograms. Since I introduced tomography into Bsoft almost two decades ago, the field has advanced significantly, requiring refinement of old algorithms and development of new ones. The current direct detectors allow us to collect data more efficiently and with better quality, progressing towards automation

  • Structural analysis and reaction mechanism of the disproportionating enzyme (D‐enzyme) from potato
    Protein Sci. (IF 3.876) Pub Date : 2020-08-18
    Kayo Imamura; Takanori Matsuura; Atsushi Nakagawa; Shinichi Kitamura; Masami Kusunoki; Takeshi Takaha; Hideaki Unno

    Starch produced by plants is a stored form of energy and is an important dietary source of calories for humans and domestic animals. Disproportionating enzyme (D‐enzyme) catalyzes intramolecular and intermolecular transglycosylation reactions of α‐1, 4‐glucan. D‐enzyme is essential in starch metabolism in the potato. We present the crystal structures of potato D‐enzyme, including two different types

  • Hsp90 chaperones have an energetic hot‐spot for binding inhibitors
    Protein Sci. (IF 3.876) Pub Date : 2020-08-19
    Reyal S. Hoxie; Timothy O. Street

    Although Hsp90‐family chaperones have been extensively targeted with ATP‐competitive inhibitors, it is unknown whether high affinity is achieved from a few highly stabilizing contacts or from many weaker contacts within the ATP‐binding pocket. A large‐scale analysis of Hsp90α:inhibitor structures shows that inhibitor hydrogen‐bonding to a conserved aspartate (D93 in Hsp90α) stands out as most universal

  • Comparing the binding properties of peptides mimicking the Envelope protein of SARS‐CoV and SARS‐CoV‐2 to the PDZ domain of the tight junction‐associated PALS1 protein
    Protein Sci. (IF 3.876) Pub Date : 2020-08-21
    Angelo Toto; Sana Ma; Francesca Malagrinò; Lorenzo Visconti; Livia Pagano; Kristian Stromgaard; Stefano Gianni

    The Envelope protein (E) is one of the four structural proteins encoded by the genome of SARS‐CoV and SARS‐CoV‐2 Coronaviruses. It is an integral membrane protein, highly expressed in the host cell, which is known to have an important role in Coronaviruses maturation, assembly and virulence. The E protein presents a PDZ‐binding motif at its C‐terminus. One of the key interactors of the E protein in

  • Using collections of structural models to predict changes of binding affinity caused by mutations in protein-protein interactions.
    Protein Sci. (IF 3.876) Pub Date : 2020-08-14
    Alberto Meseguer,Lluis Dominguez,Patricia M Bota,Joaquim Aguirre-Plans,Jaume Bonet,Narcis Fernandez-Fuentes,Baldo Oliva

    Protein–protein interactions (PPIs) in all the molecular aspects that take place both inside and outside cells. However, determining experimentally the structure and affinity of PPIs is expensive and time consuming. Therefore, the development of computational tools, as a complement to experimental methods, is fundamental. Here, we present a computational suite: MODPIN, to model and predict the changes

  • 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

  • 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 (i) significant performance and graphics enhancements; (ii) new implementations of Chimera's most highly used tools, many with further improvements; (iii) several entirely new analysis features; (iv) support for new

  • Crystal structure of the nucleotide-metabolizing enzyme NTPDase4.
    Protein Sci. (IF 3.876) Pub Date : 2020-08-06
    Alexei Gorelik,Jonathan M Labriola,Katalin Illes,Bhushan Nagar

    The ecto‐nucleoside triphosphate diphosphohydrolases (NTPDases) are a family of enzymes found on the cell surface and in the lumen of certain organelles, that are major regulators of purinergic signaling. Their intracellular roles, however, have not been clearly defined. NTPDase4 (UDPase, ENTPD4) is a Golgi protein potentially involved in nucleotide recycling as part of protein glycosylation, and is

  • Conserved tryptophan mutation disrupts structure and function of immunoglobulin domain revealing unusual tyrosine fluorescence.
    Protein Sci. (IF 3.876) Pub Date : 2020-08-14
    Ravi Vattepu,Rachel A Klausmeyer,Allan Ayella,Rahul Yadav,Joseph T Dille,Stan V Saiz,Moriah R Beck

    Immunoglobulin (Ig) domains are the most prevalent protein domain structure and share a highly conserved folding pattern; however, this structural family of proteins is also the most diverse in terms of biological roles and tissue expression. Ig domains vary significantly in amino acid sequence but share a highly conserved tryptophan in the hydrophobic core of this beta‐stranded protein. Palladin is

  • Erratum
    Protein Sci. (IF 3.876) Pub Date : 2020-09-01

    Han, M., Liao, S., Peng, X., Zhou, X., Chen, Q. and Liu, H. (2019), Selection and analyses of variants of a designed protein suggest importance of hydrophobicity of partially buried sidechains for protein stability at high temperatures. Protein Science, 28: 1437–1447. doi: 10.1002/pro.3643 In the originally published version, the name of the second author is incorrectly listed as Sanhui. The correct

  • 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

  • Domain interactions determine the conformational ensemble of the periplasmic chaperone SurA.
    Protein Sci. (IF 3.876) Pub Date : 2020-08-03
    Dagan C Marx,Mathis J Leblanc,Ashlee M Plummer,Susan Krueger,Karen G Fleming

    SurA is thought to be the most important periplasmic chaperone for outer membrane protein (OMP) biogenesis. Its structure is composed of a core region and two peptidylprolyl isomerase domains, termed P1 and P2, connected by flexible linkers. As such these three independent folding units are able to adopt a number of distinct spatial positions with respect to each other. The conformational dynamics

  • In This Issue
    Protein Sci. (IF 3.876) Pub Date : 2020-08-28

    1864 Flying blind, or just flying under the radar? The underappreciated power of de novo methods of mass spectrometric peptide identification Isabelle O'Bryon, Sarah C. Jenson, and Eric D. Merkley The capacity of liquid chromatography‐mass spectrometry to identify protein sequences is well known. But the commonly used bioinformatics techniques that match mass spectra to peptide sequences are critically

  • Flying Blind, or Just Flying Under the Radar? The Underappreciated Power of de novo Methods of Mass Spectrometric Peptide Identification.
    Protein Sci. (IF 3.876) Pub Date : 2020-07-26
    Isabelle O'Bryon,Sarah C Jenson,Eric D Merkley

    Mass spectrometry‐based proteomics is a popular and powerful method for precise and highly multiplexed protein identification. The most common method of analyzing untargeted proteomics data is called database searching, where the database is simply a collection of protein sequences from the target organism, derived from genome sequencing. Experimental peptide tandem mass spectra are compared to simplified

  • 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 A M Otsuka,Rafael S Chagas,Vitor M Almeida,Sandro R 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 (KD), which was in the micromolar range. Enzyme kinetic parameters

  • Architecture and self-assembly of the SARS-CoV-2 nucleocapsid protein.
    Protein Sci. (IF 3.876) Pub Date : 2020-07-12
    Qiaozhen Ye,Alan M V West,Steve Silletti,Kevin D Corbett

    The COVID‐2019 pandemic is the most severe acute public health threat of the twenty‐first century. To properly address this crisis with both robust testing and novel treatments, we require a deep understanding of the life cycle of the causative agent, the SARS‐CoV‐2 coronavirus. Here, we examine the architecture and self‐assembly properties of the SARS‐CoV‐2 nucleocapsid protein, which packages viral

  • Structural investigation of 2-naphthyl phenyl ether inhibitors bound to WT and Y181C reverse transcriptase highlights key features of the NNRTI binding site.
    Protein Sci. (IF 3.876) Pub Date : 2020-07-08
    Vincent N Duong,Joseph A Ippolito,Albert H Chan,Won-Gil Lee,Krasimir A Spasov,William L Jorgensen,Karen S Anderson

    Human immunodeficiency virus (HIV)‐1 remains as a global health issue that is primarily treated with highly active antiretroviral therapy, a combination of drugs that target the viral life cycle. One class of these drugs are non‐nucleoside reverse transcriptase inhibitors (NNRTIs) that target the viral reverse transcriptase (RT). First generation NNRTIs were troubled with poor pharmacological properties

  • An allosteric pathway explains beneficial fitness in yeast for long-range mutations in an essential TIM barrel enzyme.
    Protein Sci. (IF 3.876) Pub Date : 2020-07-08
    Yvonne H Chan,Konstantin B Zeldovich,C Robert Matthews

    Protein evolution proceeds by a complex response of organismal fitness to mutations that can simultaneously affect protein stability, structure, and enzymatic activity. To probe the relationship between genotype and phenotype, we chose a fundamental paradigm for protein evolution, folding, and design, the (βα)8 TIM barrel fold. Here, we demonstrate the role of long‐range allosteric interactions in

  • A humanized antibody inhibitor for cathepsin L.
    Protein Sci. (IF 3.876) Pub Date : 2020-07-19
    Xiaojing Shi,Yong Zhang

    Cathepsin L (CTSL) is a cysteine protease involved in a variety of physiological and pathological processes. Potent inhibitors against CTSL have long been sought for drug development. Due to insufficient specificity and suboptimal pharmacological properties for current CTSL inhibitors, novel agents are still required for selectively blocking CTSL activity. Here we generated a humanized antibody inhibitor

  • Using physical features of protein core packing to distinguish real proteins from decoys.
    Protein Sci. (IF 3.876) Pub Date : 2020-07-25
    Alex T Grigas,Zhe Mei,John D Treado,Zachary A Levine,Lynne Regan,Corey S O'Hern

    The ability to consistently distinguish real protein structures from computationally generated model decoys is not yet a solved problem. One route to distinguish real protein structures from decoys is to delineate the important physical features that specify a real protein. For example, it has long been appreciated that the hydrophobic cores of proteins contribute significantly to their stability.

  • Cumulative deamidations of the major lens protein γS-crystallin increase its aggregation during unfolding and oxidation.
    Protein Sci. (IF 3.876) Pub Date : 2020-07-22
    Calvin J Vetter,David C Thorn,Samuel G Wheeler,Charlie Mundorff,Kate Halverson,Thomas E Wales,Ujwal Shinde,John R Engen,Larry L David,John A Carver,Kirsten J Lampi

    Age‐related lens cataract is the major cause of blindness worldwide. The mechanisms whereby crystallins, the predominant lens proteins, assemble into large aggregates that scatter light within the lens, and cause cataract, are poorly understood. Due to the lack of protein turnover in the lens, crystallins are long‐lived. A major crystallin, γS, is heavily modified by deamidation, in particular at surface‐exposed

  • Structure-guided evolution of Green2 towards photostability and quantum yield enhancement by F145Y substitution.
    Protein Sci. (IF 3.876) Pub Date : 2020-07-26
    Tingting Sun,Tianpeng Li,Ke Yi,Xiaolian Gao

    Quantum yield is a determinant for fluorescent protein (FP) applications and enhancing FP brightness through gene engineering is still a challenge. Green2, our de novo FP synthesized by microfluidic picoarray and cloning, has a significantly lower quantum yield than enhanced green FP, though they have high homology and share the same chromophore. To increase its quantum yield, we introduced an F145Y

  • Drivers of recombinant soluble influenza A virus hemagglutinin and neuraminidase expression in mammalian cells.
    Protein Sci. (IF 3.876) Pub Date : 2020-07-25
    Roosmarijn van der Woude,Hannah L Turner,Ilhan Tomris,Kim M Bouwman,Andrew B Ward,Robert P de Vries

    Recombinant soluble trimeric influenza A virus hemagglutinins (HA) and tetrameric neuraminidases (NAs) have proven to be excellent tools to decipher biological properties. Receptor binding and sialic acid cleavage by recombinant proteins correlate satisfactorily compared to whole viruses. Expression of HA and NA can be achieved in a plethora of different laboratory hosts. For immunological and receptor

  • Tumorigenic p53 mutants undergo common structural disruptions including conversion to α-sheet structure.
    Protein Sci. (IF 3.876) Pub Date : 2020-07-26
    Dennis Bromley,Valerie Daggett

    The p53 protein is a commonly studied cancer target because of its role in tumor suppression. Unfortunately, it is susceptible to mutation‐associated loss of function; approximately 50% of cancers are associated with mutations to p53, the majority of which are located in the central DNA‐binding domain. Here, we report molecular dynamics simulations of wild‐type (WT) p53 and 20 different mutants, including

  • Crystal structure of a GH1 β-glucosidase from Hamamotoa singularis.
    Protein Sci. (IF 3.876) Pub Date : 2020-07-26
    Ryo Uehara,Riki Iwamoto,Sayaka Aoki,Takuya Yoshizawa,Kazufumi Takano,Hiroyoshi Matsumura,Shun-Ichi Tanaka

    A GH1 β‐glucosidase from the fungus Hamamotoa singularis (HsBglA) has high transgalactosylation activity and efficiently converts lactose to galactooligosaccharides. Consequently, HsBglA is among the most widely used enzymes for industrial galactooligosaccharide production. Here, we present the first crystal structures of HsBglA with and without 4′‐galactosyllactose, a tri‐galactooligosaccharide, at

  • Structure and function of the juxtamembrane GAF domain of potassium biosensor KdpD.
    Protein Sci. (IF 3.876) Pub Date : 2020-07-26
    Shivesh Kumar,Richard E Gillilan,Dinesh A Yernool

    KdpD/KdpE two‐component signaling system regulates expression of a high affinity potassium transporter responsible for potassium homeostasis. The C‐terminal module of KdpD consists of a GAF domain linked to a histidine kinase domain. Whereas certain GAF domains act as regulators by binding cyclic nucleotides, the role of the juxtamembrane GAF domain in KdpD is unknown. We report the high‐resolution

  • Cotranslational folding of alkaline phosphatase in the periplasm of Escherichia coli.
    Protein Sci. (IF 3.876) Pub Date : 2020-08-13
    Rageia Elfageih,Alexandros Karyolaimos,Grant Kemp,Jan-Willem de Gier,Gunnar von Heijne,Renuka Kudva

    Cotranslational protein folding studies using Force Profile Analysis, a method where the SecM translational arrest peptide is used to detect folding‐induced forces acting on the nascent polypeptide, have so far been limited mainly to small domains of cytosolic proteins that fold in close proximity to the translating ribosome. In this study, we investigate the cotranslational folding of the periplasmic

  • Doses for experiments with microbeams and microcrystals: Monte Carlo simulations in RADDOSE-3D.
    Protein Sci. (IF 3.876) Pub Date : 2020-07-30
    Joshua L Dickerson,Elspeth F Garman

    Increasingly, microbeams and microcrystals are being used for macromolecular crystallography (MX) experiments at synchrotrons. However, radiation damage remains a major concern since it is a fundamental limiting factor affecting the success of macromolecular structure determination. The rate of radiation damage at cryotemperatures is known to be proportional to the absorbed dose, so to optimize experimental

  • The Bio3D packages for structural bioinformatics.
    Protein Sci. (IF 3.876) Pub Date : 2020-07-30
    Barry J Grant,Lars Skjaerven,Xin-Qiu Yao

    Bio3D is a family of R packages for the analysis of biomolecular sequence, structure, and dynamics. Major functionality includes biomolecular database searching and retrieval, sequence and structure conservation analysis, ensemble normal mode analysis, protein structure and correlation network analysis, principal component, and related multivariate analysis methods. Here, we review recent package developments

  • The High-Resolution Structure of a UDP-l-Rhamnose Synthase from Acanthamoeba polyphaga Mimivirus.
    Protein Sci. (IF 3.876) Pub Date : 2020-08-14
    Nicholas J Bockhaus,Justin D Ferek,James B Thoden,Hazel M Holden

    For the field of virology, perhaps one of the most paradigm‐shifting events so far in the 21st century was the identification of the giant double‐stranded DNA virus that infects amoebae. Remarkably, this virus, known as Mimivirus, has a genome that encodes for nearly 1000 proteins, some of which are involved in the biosynthesis of unusual sugars. Indeed, the virus is coated by a layer of glycosylated

  • In This Issue
    Protein Sci. (IF 3.876) Pub Date : 2020-07-24

    1698 Harnessing synthetic biology to enhance heterologous protein expression Shlomo Zarzhitsky, Alex Jiang, Elizabeth E. Stanley, and Michael H. Hecht Expressing heterologous proteins in microbial hosts is a core technology for protein science. However, heterologous protein expression often produces low yields and/or misfolded products. To overcome these challenges, a protein of interest (POI) can

  • Harnessing synthetic biology to enhance heterologous protein expression.
    Protein Sci. (IF 3.876) Pub Date : 2020-06-22
    Shlomo Zarzhitsky,Alex Jiang,Elizabeth E Stanley,Michael H 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 require 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

  • 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

  • A mechanistic view of enzyme evolution.
    Protein Sci. (IF 3.876) Pub Date : 2020-06-19
    Gloria Yang,Charlotte M 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

  • 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 (AD) 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

  • 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

  • Discriminating changes in protein structure using tyrosine conjugation.
    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

  • 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: (a) unique to a particular domain, family, or superfamily or (b) 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

  • Cryo-electron microscopy 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

  • (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 L 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

  • 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

  • Solution structure of the 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 an 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. Moreover

  • The long form of pVHL is artifactually 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

  • PyXlinkViewer: A flexible tool for visualization 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 yield 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

  • 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

  • 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

  • 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

  • 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

  • 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

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