DOCSLIB.ORG

Influenza Neuraminidase

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Influenza Neuraminidase Hao Wang Influenza Neuraminidase Novel Mechanisms of Influenza NA that Enable Adaptation and Influenza Neuraminidase Promote Diversification Hao Wang ISBN 978-91-7911-214-1 NA claw machine Department of Biochemistry and Biophysics Doctoral Thesis in Biochemistry at Stockholm University, Sweden 2020 Influenza Neuraminidase Novel mechanisms of influenza NA that enable adaptation and promote diversification Hao Wang Academic dissertation for the Degree of Doctor of Philosophy in Biochemistry at Stockholm University to be publicly defended on Tuesday 29 September 2020 at 14.00 in via Zoom. A link will be published on https://www.dbb.su.se. Abstract Influenza A viruses (IAVs) are one of the most common human respiratory pathogens and are largely responsible for the seasonal influenza epidemics that cause mild to severe disease. The two IAV glycoproteins, hemagglutinin (HA or H) and neuraminidase (NA or N), serve as the major surface antigens and also are the main determinants of infectivity, pathogenicity and transmissibility. Due to the high abundance in the IAV envelope and its defined functions of mediating cell binding and viral entry, current influenza vaccines have primarily been developed based on HA. The less abundant NA is a receptor-destroying enzyme that facilitates virion release from the infected cell and the escape from decoy receptors during the entry process. Despite these important roles for infection, NA has been largely neglected in vaccines because of its low abundance and labile properties. The work in this thesis involves several studies that have primarily focused on establishing a general overview of NA maturation and providing a biochemical assessment of the enzymatic properties in the NAs from circulating H1N1 IAVs. The results from these studies show that the membrane integration of a class of NAs is dependent on the synthesis of its long C-terminus, NA tetramerization is coordinated by its N-terminal transmembrane domain (TMD) and the distal enzymatic head domain, NA stability changes are related to intrinsic and extrinsic determinants, and that the N-linked glycosylation sites on the NA head domain contribute to viral incorporation. In addition, we demonstrated that NA oligomeric structure possesses sufficient plasticity to allow the formation of heterotetramers, which increases the tolerance for suboptimal substitutions and contributes to the diversification of its enzymatic properties. Together, these results provide new insights into the NA maturation process and the biochemical mechanisms that are responsible for the NA property differences that are observed in circulating H1N1 IAVs. Keywords: Influenza, IAV, neuraminidase, transmembrane domain, the central Ca2+ binding site, heterotetrameric formation, viral incorporation, evolution, adaptation, diversification. Stockholm 2020 http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-182612 ISBN 978-91-7911-214-1 ISBN 978-91-7911-215-8 Department of Biochemistry and Biophysics Stockholm University, 106 91 Stockholm INFLUENZA NEURAMINIDASE Hao Wang Influenza Neuraminidase Novel Mechanisms of Influenza NA that Enable Adaptation and Promote Diversification Hao Wang ©Hao Wang, Stockholm University 2020 ISBN print 978-91-7911-214-1 ISBN PDF 978-91-7911-215-8 Printed in Sweden by Universitetsservice US-AB, Stockholm 2020 Dedication to my family: my parents, mother-in- law, wife, daughter and son. List of publications I. Type II Transmembrane Domain Hydrophobicity Dictates the Co- translational Dependence for Inversion. Dou D, da Silva DV, Nordholm J, Wang H, Daniels R. Mol Biol Cell. 2014 Nov 1;25(21):3363-74. doi: 10.1091/mbc.E14-04-0874 II. The Influenza Virus Neuraminidase Protein Transmembrane and Head Domains Have Coevolved. da Silva DV, Nordholm J, Dou D, Wang H, Rossman JS, Daniels R. J Virol. 2015 Jan 15;89(2):1094-104. doi: 10.1128/JVI.02005-14 III. Structural restrictions for influenza neuraminidase activity promote adaptation and diversification. Wang H, Dou D, Östbye H, Revol R, Daniels R. Nature Microbiol- ogy. 2019 Aug 26; doi.org/10.1038/s41564-019-0537-z IV. Conserved N-linked glycans on the influenza NA head domain con- tribute to viral incorporation but are not essential for H1N1 replica- tion. Manuscript Östbye H*, Wang H*, Martinez MR., Gao J., Daniels R. * Both authors contributed equally to this work Publications not included in this thesis I. Analysis of IAV Replication and Co-infection Dynamics by a Versa- tile RNA Viral Genome Labeling Method. Dou D, Hernández-Neuta I, Wang H, Östbye H, Qian X, Thiele S, Resa-Infante P, Kouassi NM, Sender V, Hentrich K, Mellroth P, Hen- riques-Normark B, Gabriel G, Nilsson M, Daniels R. Cell Rep. 2017 Jul 5;20(1):251-263. doi: 10.1016/j.celrep.2017.06.021. II. Translational Regulation of Viral Secretory Proteins by the 5' Cod- ing Regions and a Viral RNA-binding Protein. Nordholm J, Petitou J, Östbye H, da Silva DV, Dou D, Wang H, Dan- iels R. J Cell Biol. 2017 Aug 7;216(8):2283-2293. doi: 10.1083/jcb.201702102 III. Multiple nuclear-replicating viruses require the stress- induced pro- tein ZC3H11A for efficient growth. Shady Younis, Wael Kamel, Tina Falkeborn, H Wang, Di Yue, Rob- ert Daniels, Magnus Essand, Jorma Hinkula, Göran Akusjärvi and Leif Andersson. PNAS. 2018 Apr 17;115(16): E3808-E3816. doi: 10.1073/pnas.1722333115 IV. Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement. Dou D, Revol R, Östbye H, Wang H, Daniels R. Front Immunol. 2018 Jul 20;9:1581. doi: 10.3389/fimmu.2018.01581 Abstract Influenza A viruses (IAVs) are one of the most common human respiratory pathogens and are largely responsible for the seasonal influenza epidemics that cause mild to severe disease. The two IAV glycoproteins, hemagglutinin (HA or H) and neuraminidase (NA or N), serve as the major surface antigens and also are the main determinants of infectivity, pathogenicity and transmis- sibility. Due to the high abundance in the IAV envelope and its defined func- tions of mediating cell binding and viral entry, current influenza vaccines have primarily been developed based on HA. The less abundant NA is a receptor- destroying enzyme that facilitates virion release from the infected cell and the escape from decoy receptors during the entry process. Despite these important roles for infection, NA has been largely neglected in vaccines because of its low abundance and labile properties. The work in this thesis involves several studies that have primarily focused on establishing a general overview of NA maturation and providing a bio- chemical assessment of the enzymatic properties in the NAs from circulating H1N1 IAVs. The results from these studies show that the membrane integra- tion of a class of NAs is dependent on the synthesis of its long C-terminus, NA tetramerization is coordinated by its N-terminal transmembrane domain (TMD) and the distal enzymatic head domain, NA stability changes are related to intrinsic and extrinsic determinants, and that the N-linked glycosylation sites on the NA head domain contribute to viral incorporation. In addition, we demonstrated that NA oligomeric structure possesses sufficient plasticity to allow the formation of heterotetramers, which increases the tolerance for suboptimal substitutions and contributes to the diversification of its enzymatic properties. Together, these results provide new insights into the NA maturation pro- cess and the biochemical mechanisms that are responsible for the NA property differences that are observed in circulating H1N1 IAVs. Contents Influenza A virus ............................................................................... 1 IAV subtypes ......................................................................................... 2 IAV life cycle ........................................................................................ 2 IAV Neuraminidase ........................................................................... 7 Structure ................................................................................................ 8 Synthesis and Maturation ..................................................................... 11 Functions ............................................................................................. 14 NA as antiviral target and a vaccine antigen ......................................... 17 Results summary ............................................................................. 21 Conclusions and future perspectives ................................................ 25 Sammanfattning på svenska ............................................................. 29 Acknowledgments ........................................................................... 31 References ....................................................................................... 33 Abbreviations ADCC antibody-dependent cell-mediated cytotoxicity ADPC antibody-dependent phagocytosis CRM1 chromosomal maintenance 1 cRNA complementary RNA DANA 2,3-dehydro-2-deoxy-N-acetylneuraminic acid ER endoplasmic reticulum HA hemagglutinin IAV Influenza A virus M1 matrix protein 1 M2 matrix protein 2 MAbs monoclonal antibodies NA neuraminidase NAIs neuraminidase inhibitors NK natural killer NLS nuclear localization sequence NP nucleoprotein OST oligosaccharyltransferase PA polymerase acidic protein PB1 polymerase basic protein 1 PB2 polymerase basic protein 2 SA sialic acid SRP signal recognition particle SS ER signal sequence TMD transmembrane domain vRNP viral ribonucleoprotein vRNA viral RNA Influenza A virus IAVs are one of the
Load more

Recommended publications
  • Identification of Hsc70 As an Influenza Virus Matrix Protein (M1)
    FEBS Letters 580 (2006) 5785–5790 Identification of Hsc70 as an influenza virus matrix protein (M1) binding factor involved in the virus life cycle Ken Watanabea, Takayuki Fusea, Issay Asanoa, Fujiko Tsukaharab, Yoshiro Marub, Kyosuke Nagatac, Kaio Kitazatoa, Nobuyuki Kobayashia,* a Laboratory of Molecular Biology of Infectious Agents, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan b Department of Pharmacology, Tokyo Women’s Medical University, School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan c Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan Received 22 August 2006; revised 13 September 2006; accepted 15 September 2006 Available online 27 September 2006 Edited by Felix Wieland nuclear export signal (NES), thus mechanism of M1-mediated Abstract Influenza virus matrix protein 1 (M1) has been shown to play a crucial role in the virus replication, assembly and bud- nuclear export of vRNP is still not well understood. ding. We identified heat shock cognate protein 70 (Hsc70) as a We herein identify heat shock cognate protein 70 (Hsc70), a M1 binding protein by immunoprecipitation and MALDI-TOF constitutive form of Hsp70 family protein, as an host factor(s) MS. The C terminal domain of M1 interacts with Hsc70. We which bind to M1 in infected cells by matrix-assisted laser found that Hsc70 does not correlate with the transport of M1 desorption ionization-time of flight mass spectrometry (MAL- to the nucleus, however, it does inhibit the nuclear export of DI-TOF MS). Heat shock proteins (Hsps) were induced by M1 and NP, thus resulting in the inhibition of viral production.
    [Show full text]
  • Distinct Contributions of Different Domains Within the HIV-1 Gag
    viruses Article Distinct Contributions of Different Domains within the HIV-1 Gag Polyprotein to Specific and Nonspecific Interactions with RNA Tomas Kroupa , Siddhartha A. K. Datta and Alan Rein * HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; [email protected] (T.K.); [email protected] (S.A.K.D.) * Correspondence: [email protected] Received: 24 February 2020; Accepted: 31 March 2020; Published: 2 April 2020 Abstract: Viral genomic RNA is packaged into virions with high specificity and selectivity. However, in vitro the Gag specificity towards viral RNA is obscured when measured in buffers containing physiological salt. Interestingly, when the binding is challenged by increased salt concentration, the addition of competing RNAs, or introducing mutations to Gag protein, the specificity towards viral RNA becomes detectable. The objective of this work was to examine the contributions of the individual HIV-1 Gag polyprotein domains to nonspecific and specific RNA binding and stability of the initial protein-RNA complexes. Using a panel of Gag proteins with mutations disabling different Gag-Gag or Gag-RNA interfaces, we investigated the distinct contributions of individual domains which distinguish the binding to viral and nonviral RNA by measuring the binding of the proteins to RNAs. We measured the binding affinity in near-physiological salt concentration, and then challenged the binding by increasing the ionic strength to suppress the electrostatic interactions and reveal the contribution of specific Gag–RNA and Gag–Gag interactions. Surprisingly, we observed that Gag dimerization and the highly basic region in the matrix domain contribute significantly to the specificity of viral RNA binding.
    [Show full text]
  • How Influenza Virus Uses Host Cell Pathways During Uncoating
    cells Review How Influenza Virus Uses Host Cell Pathways during Uncoating Etori Aguiar Moreira 1 , Yohei Yamauchi 2 and Patrick Matthias 1,3,* 1 Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; [email protected] 2 Faculty of Life Sciences, School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK; [email protected] 3 Faculty of Sciences, University of Basel, 4031 Basel, Switzerland * Correspondence: [email protected] Abstract: Influenza is a zoonotic respiratory disease of major public health interest due to its pan- demic potential, and a threat to animals and the human population. The influenza A virus genome consists of eight single-stranded RNA segments sequestered within a protein capsid and a lipid bilayer envelope. During host cell entry, cellular cues contribute to viral conformational changes that promote critical events such as fusion with late endosomes, capsid uncoating and viral genome release into the cytosol. In this focused review, we concisely describe the virus infection cycle and highlight the recent findings of host cell pathways and cytosolic proteins that assist influenza uncoating during host cell entry. Keywords: influenza; capsid uncoating; HDAC6; ubiquitin; EPS8; TNPO1; pandemic; M1; virus– host interaction Citation: Moreira, E.A.; Yamauchi, Y.; Matthias, P. How Influenza Virus Uses Host Cell Pathways during 1. Introduction Uncoating. Cells 2021, 10, 1722. Viruses are microscopic parasites that, unable to self-replicate, subvert a host cell https://doi.org/10.3390/ for their replication and propagation. Despite their apparent simplicity, they can cause cells10071722 severe diseases and even pose pandemic threats [1–3].
    [Show full text]
  • Assessment of the Interaction Between the Human
    VARIATIONS IN THE V3 CROWN OF HIV-1 ENVELOPE IMPACT AFFINITY FOR CCR5 AND AFFECT ENTRY AND REPLICATIVE FITNESS By MICHAEL ANDREW LOBRITZ Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Dissertation advisor: Eric J. Arts, Ph.D. Department of Molecular Biology and Microbiology CASE WESTERN RESERVE UNIVERSITY August 2007 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the dissertation of ______________________________________________________ candidate for the Ph.D. degree *. (signed)_______________________________________________ (chair of the committee) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. Table of Contents Chapter 1: Introduction........................................................................................................................16 1.A. HIV and AIDS..............................................................................................17 1.B. Retroviruses: Structure, Organization, and Replication...............................20 1.B.1. HIV-1 Genome...............................................................................20 1.B.2. HIV-1 Particle................................................................................23
    [Show full text]
  • Replication of HIV-1 Envelope Protein Cytoplasmic Domain Variants in Permissive and Restrictive Cells T
    Virology 538 (2019) 1–10 Contents lists available at ScienceDirect Virology journal homepage: www.elsevier.com/locate/virology Replication of HIV-1 envelope protein cytoplasmic domain variants in permissive and restrictive cells T ∗ August O. Staubus, Ayna Alfadhli, Robin Lid Barklis, Eric Barklis Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA ARTICLE INFO ABSTRACT Keywords: Wild type (WT) HIV-1 envelope (Env) protein cytoplasmic tails (CTs) appear to be composed of membrane- HIV-1 proximal, N-terminal unstructured regions, and three C-terminal amphipathic helices. Previous studies have Replication shown that WT and CT-deleted (ΔCT) Env proteins are incorporated into virus particles via different mechan- Envelope protein isms. WT Env proteins traffic to cell plasma membranes (PMs), are rapidly internalized, recycle to PMs, and are Cytoplasmic tail incorporated into virions in permissive and restrictive cells in a Gag matrix (MA) protein-dependent fashion. In contrast, previously described ΔCT proteins do not appear to be internalized after their arrival to PMs, and do not require MA, but are only incorporated into virions in permissive cell lines. We have analyzed a new set of HIV-1 CT variants with respect to their replication in permissive and restrictive cells. Our results provide novel details as to how CT elements regulate HIV-1 Env protein function. 1. Introduction et al., 2018; Ohno et al., 1997; Wyss et al., 2001). Internalized Env proteins either are shunted off to lysosomes for degradation, or return The pathways by which HIV-1 envelope (Env) proteins become in- to PMs on recycling endosomes in a pathway that is dependent, in corporated into virions are complicated and incompletely elucidated certain cell types, on the Rab11 coupling protein FIP1C (Qi et al., 2013, (Checkley et al., 2011).
    [Show full text]
  • Phosphorylation of the M2 Protein of Influenza a Virus Is Not Essential for Virus Viability
    VIROLOGY 252, 54±64 (1998) ARTICLE NO. VY989384 Phosphorylation of the M2 Protein of Influenza A Virus Is Not Essential for Virus Viability Joanne M. Thomas, Mark P. Stevens, Neil Percy,1 and Wendy S. Barclay2 School of Animal and Microbial Sciences, University of Reading, Whiteknights, UK RG6 6AJ Received May 14, 1998; returned to author for revision June 12, 1998; accepted August 18, 1998 M2 is a minor component of the influenza A virus envelope. The cytoplasmic tail of the M2 protein is posttranslationally modified in the infected cell by palmitylation and phosphorylation. The primary site for phosphorylation of the M2 cytoplasmic tail is serine 64, which is highly conserved yet not required for the activity of the M2 ion channel. Using an exogenous incorporation assay, we have shown that incorporation of M2 into virus particles is type-specific and does not require phosphorylation of the cytoplasmic tail. In addition, phosphorylation of the cytoplasmic tail is not required for the directional transport of M2 in polarized MDCK cells. Using a reverse genetics and reassortment procedure, we generated a virus (Ra) specifically mutated in segment 7 such that the M2 cytoplasmic tail could no longer be phosphorylated. The virus was found to grow as well as wild-type virus in tissue culture and in eggs, was stable on passage in these systems, and possessed no second-site mutations in the engineered RNA segment. In vivo Ra replicated in Balb/c mice at least as well as the parent strain A/WSN/33. These studies indicate that phosphorylation of the M2 cytoplasmic tail is not required for in vitro or in vivo replication of influenza A virus.
    [Show full text]
  • Respiratory Syncytial Virus and Coronaviruses
    Chapter 3 Structural and Functional Aspects of Viroporins in Human Respiratory Viruses: Respiratory Syncytial Virus and Coronaviruses Wahyu Surya, Montserrat Samsó and Jaume Torres Additional information is available at the end of the chapter http://dx.doi.org/10.5772/53957 1. Introduction Viroporins are an increasingly recognized class of small viral membrane proteins (~60-120 amino acids) which oligomerize to produce hydrophilic pores at the membranes of virus- infected cells [1]. The existence of ‘viroporins’ was proposed more than 30 years ago after observing enhanced membrane permeability in infected cells [2]. These proteins form oligomers of defined size, and can act as proton or ion channels, and in general enhancing membrane permeability in the host [3]. Even though viroporins are not essential for the rep‐ lication of viruses, their absence results in attenuated or weakened viruses or changes in tropism (organ localization) and therefore diminished pathological effects [4, 5]. In addition to having one – sometimes two – α-helical transmembrane (TM) domain(s), viro‐ porins usually contain additional extramembrane regions that are able to make contacts with viral or host proteins. Indeed, the network of interactions of viroporins with other viral or cellular proteins is key to understand the regulation of viral protein trafficking through the vesicle system, viral morphogenesis and pathogenicity. In general, viroporins participate in the entry or release of viral particles into or out of cells, and membrane permeabilization may be a desirable functionality for the virus. Indeed, sev‐ eral viral proteins that are not viroporins are known to affect membrane permeabilization, e.g., A38L protein of vaccinia virus, a 33-kDa glycoprotein that allows Ca2+ influx and indu‐ ces necrosis in infected cells [6].
    [Show full text]
  • APICAL M2 PROTEIN IS REQUIRED for EFFICIENT INFLUENZA a VIRUS REPLICATION by Nicholas Wohlgemuth a Dissertation Submitted To
    APICAL M2 PROTEIN IS REQUIRED FOR EFFICIENT INFLUENZA A VIRUS REPLICATION by Nicholas Wohlgemuth A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland October, 2017 © Nicholas Wohlgemuth 2017 All rights reserved ABSTRACT Influenza virus infections are a major public health burden around the world. This dissertation examines the influenza A virus M2 protein and how it can contribute to a better understanding of influenza virus biology and improve vaccination strategies. M2 is a member of the viroporin class of virus proteins characterized by their predicted ion channel activity. While traditionally studied only for their ion channel activities, viroporins frequently contain long cytoplasmic tails that play important roles in virus replication and disruption of cellular function. The currently licensed live, attenuated influenza vaccine (LAIV) contains a mutation in the M segment coding sequence of the backbone virus which confers a missense mutation (alanine to serine) in the M2 gene at amino acid position 86. Previously discounted for not showing a phenotype in immortalized cell lines, this mutation contributes to both the attenuation and temperature sensitivity phenotypes of LAIV in primary human nasal epithelial cells. Furthermore, viruses encoding serine at M2 position 86 induced greater IFN-λ responses at early times post infection. Reversing mutations such as this, and otherwise altering LAIV’s ability to replicate in vivo, could result in an improved LAIV development strategy. Influenza viruses infect at and egress from the apical plasma membrane of airway epithelial cells. Accordingly, the virus transmembrane proteins, HA, NA, and M2, are all targeted to the apical plasma membrane ii and contribute to egress.
    [Show full text]
  • Investigation of the C-Terminal Helix of HIV-1 Matrix: a Region Essential for Multiple Functions in the Viral Life Cycle: a Dissertation
    University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2011-07-10 Investigation of the C-Terminal Helix of HIV-1 Matrix: A Region Essential for Multiple Functions in the Viral Life Cycle: A Dissertation Laura A. Brandano University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Biological Factors Commons, Genetic Phenomena Commons, Immunology and Infectious Disease Commons, Therapeutics Commons, Virology Commons, Virus Diseases Commons, and the Viruses Commons Repository Citation Brandano LA. (2011). Investigation of the C-Terminal Helix of HIV-1 Matrix: A Region Essential for Multiple Functions in the Viral Life Cycle: A Dissertation. GSBS Dissertations and Theses. https://doi.org/ 10.13028/5zmj-9x81. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/552 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. i INVESTIGATION OF THE C-TERMINAL HELIX OF HIV-1 MATRIX: A REGION ESSENTIAL FOR MULTIPLE FUNCTIONS IN THE VIRAL LIFE CYCLE A Dissertation Presented by Laura A. Brandano Submitted to the Faculty of the University of Massachusetts Graduate School of Biomedical Sciences, Worcester in partial fulfillment of the requirements for the degree of DOCTOR
    [Show full text]
  • XFEL Structures of the Influenza M2 Proton Channel: SPECIAL FEATURE Room Temperature Water Networks and Insights Into Proton Conduction
    XFEL structures of the influenza M2 proton channel: SPECIAL FEATURE Room temperature water networks and insights into proton conduction Jessica L. Thomastona, Rahel A. Woldeyesb, Takanori Nakane (中根 崇智)c, Ayumi Yamashitad, Tomoyuki Tanakad, Kotaro Koiwaie, Aaron S. Brewsterf, Benjamin A. Baradb, Yujie Cheng, Thomas Lemmina, Monarin Uervirojnangkoornh,i,j,k,l, Toshi Arimad, Jun Kobayashid, Tetsuya Masudad,m, Mamoru Suzukid,n, Michihiro Sugaharad, Nicholas K. Sauterf, Rie Tanakad, Osamu Nurekic, Kensuke Tonoo, Yasumasa Jotio, Eriko Nangod, So Iwatad,p, Fumiaki Yumotoe, James S. Fraserb, and William F. DeGradoa,1 aDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158; bDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158; cDepartment of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan; dSPring-8 Angstrom Compact Free Electron Laser (SACLA) Science Research Group, RIKEN SPring-8 Center, Saitama 351-0198, Japan; eStructural Biology Research Center, High Energy Accelerator Research Organization (KEK), Ibaraki 305-0801, Japan; fMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720; gSchool of Applied and Engineering Physics, Cornell University, Ithaca, NY 14853; hDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305; iHoward Hughes Medical Institute, Stanford University, Stanford, CA 94305; jDepartment of Neurology
    [Show full text]
  • Virus Entry, Assembly, Budding, and Membrane Rafts Nathalie Chazal, Denis Gerlier
    Virus Entry, Assembly, Budding, and Membrane Rafts Nathalie Chazal, Denis Gerlier To cite this version: Nathalie Chazal, Denis Gerlier. Virus Entry, Assembly, Budding, and Membrane Rafts. Microbi- ology and Molecular Biology Reviews, American Society for Microbiology, 2003, 67 (2), pp.226-237. 10.1128/MMBR.67.2.226-237.2003. hal-02147208 HAL Id: hal-02147208 https://hal.archives-ouvertes.fr/hal-02147208 Submitted on 7 Jun 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, June 2003, p. 226–237 Vol. 67, No. 2 1092-2172/03/$08.00ϩ0 DOI: 10.1128/MMBR.67.2.226–237.2003 Copyright © 2003, American Society for Microbiology. All Rights Reserved. Virus Entry, Assembly, Budding, and Membrane Rafts Nathalie Chazal1* and Denis Gerlier2 Immunologie-Virologie, EA 3038, Universite´Paul Sabatier, 31062 Toulouse,1 and Immunite´& Infections Virales, CNRS-UCBL UMR 5537, IFR Laennec, 69372 Lyon Cedex 08,2 France INTRODUCTION .......................................................................................................................................................226
    [Show full text]
  • Influenza Virus Matrix Protein M1 Preserves Its Conformation with Ph
    www.nature.com/scientificreports OPEN Infuenza virus Matrix Protein M1 preserves its conformation with pH, changing multimerization Received: 8 August 2017 Accepted: 21 November 2017 state at the priming stage due to Published: xx xx xxxx electrostatics Eleonora V. Shtykova1,2, Liubov A. Dadinova1, Natalia V. Fedorova3, Andrey E. Golanikov1, Elena N. Bogacheva2, Alexander L. Ksenofontov3, Liudmila A. Baratova3, Liudmila A. Shilova4,5, Vsevolod Yu. Tashkin4, Timur R. Galimzyanov4,6, Cy M. Jefries 7, Dmitri I. Svergun7 & Oleg V. Batishchev 4,5 Infuenza A virus matrix protein M1 plays an essential role in the virus lifecycle, but its functional and structural properties are not entirely defned. Here we employed small-angle X-ray scattering, atomic force microscopy and zeta-potential measurements to characterize the overall structure and association behavior of the full-length M1 at diferent pH conditions. We demonstrate that the protein consists of a globular N-terminal domain and a fexible C-terminal extension. The globular N-terminal domain of M1 monomers appears preserved in the range of pH from 4.0 to 6.8, while the C-terminal domain remains fexible and the tendency to form multimers changes dramatically. We found that the protein multimerization process is reversible, whereby the binding between M1 molecules starts to break around pH 6. A predicted electrostatic model of M1 self-assembly at diferent pH revealed a good agreement with zeta-potential measurements, allowing one to assess the role of M1 domains in M1-M1 and M1-lipid interactions. Together with the protein sequence analysis, these results provide insights into the mechanism of M1 scafold formation and the major role of the fexible and disordered C-terminal domain in this process.
    [Show full text]