Structure and Dynamics of Influenza M2 Proton Channels from Solid-State NMR By
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Multidimensional Solid-State NMR Spectroscopy of Plant Cell Walls
Solid State Nuclear Magnetic Resonance 78 (2016) 56–63' Contents lists available at ScienceDirect Solid State Nuclear Magnetic Resonance journal homepage: www.elsevier.com/locate/ssnmr Trends Multidimensional solid-state NMR spectroscopy of plant cell walls Tuo Wang, Pyae Phyo, Mei Hong n Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States article info abstract Article history: Plant biomass has become an important source of bio-renewable energy in modern society. The mole- Received 18 July 2016 cular structure of plant cell walls is difficult to characterize by most atomic-resolution techniques due to Received in revised form the insoluble and disordered nature of the cell wall. Solid-state NMR (SSNMR) spectroscopy is uniquely 9 August 2016 suited for studying native hydrated plant cell walls at the molecular level with chemical resolution. Accepted 12 August 2016 Significant progress has been made in the last five years to elucidate the molecular structures and in- Available online 13 August 2016 teractions of cellulose and matrix polysaccharides in plant cell walls. These studies have focused on Keywords: primary cell walls of growing plants in both the dicotyledonous and grass families, as represented by the Cellulose model plants Arabidopsis thaliana, Brachypodium distachyon, and Zea mays. To date, these SSNMR results Matrix polysaccharide have shown that 1) cellulose, hemicellulose, and pectins form a single network in the primary cell wall; Expansin 2) in dicot cell walls, the protein expansin targets the hemicellulose-enriched region of the cellulose Lignin fi Magic-angle spinning micro bril for its wall-loosening function; and 3) primary wall cellulose has polymorphic structures that Multidimensional correlation are distinct from the microbial cellulose structures. -
Symposium on Viral Membrane Proteins
Viral Membrane Proteins ‐ Shanghai 2011 交叉学科论坛 Symposium for Advanced Studies 第二十七期:病毒离子通道蛋白的结构与功能研讨会 Symposium on Viral Membrane Proteins 主办单位:中国科学院上海交叉学科研究中心 承办单位:上海巴斯德研究所 1 Viral Membrane Proteins ‐ Shanghai 2011 Symposium on Viral Membrane Proteins Shanghai Institute for Advanced Studies, CAS Institut Pasteur of Shanghai,CAS 30.11. – 2.12 2011 Shanghai, China 2 Viral Membrane Proteins ‐ Shanghai 2011 Schedule: Wednesday, 30th of November 2011 Morning Arrival Thursday, 1st of December 2011 8:00 Arrival 9:00 Welcome Bing Sun, Co-Director, Pasteur Institute Shanghai 9: 10 – 9:35 Bing Sun, Pasteur Institute Shanghai Ion channel study and drug target fuction research of coronavirus 3a like protein. 9:35 – 10:00 Tim Cross, Tallahassee, USA The proton conducting mechanism and structure of M2 proton channel in lipid bilayers. 10:00 – 10:25 Shy Arkin, Jerusalem, IL A backbone structure of SARS Coronavirus E protein based on Isotope edited FTIR, X-ray reflectivity and biochemical analysis. 10:20 – 10:45 Coffee Break 10:45 – 11:10 Rainer Fink, Heidelberg, DE Elektromechanical coupling in muscle: a viral target? 11:10 – 11:35 Yechiel Shai, Rehovot, IL The interplay between HIV1 fusion peptide, the transmembrane domain and the T-cell receptor in immunosuppression. 11:35 – 12:00 Christoph Cremer, Mainz and Heidelberg University, DE Super-resolution Fluorescence imaging of cellular and viral nanostructures. 12:00 – 13:30 Lunch Break 3 Viral Membrane Proteins ‐ Shanghai 2011 13:30 – 13:55 Jung-Hsin Lin, National Taiwan University Robust Scoring Functions for Protein-Ligand Interactions with Quantum Chemical Charge Models. 13:55 – 14:20 Martin Ulmschneider, Irvine, USA Towards in-silico assembly of viral channels: the trials and tribulations of Influenza M2 tetramerization. -
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]. -
Mechanisms of Action of Novel Influenza A/M2 Viroporin Inhibitors Derived from Hexamethylene Amiloride S
Supplemental material to this article can be found at: http://molpharm.aspetjournals.org/content/suppl/2016/05/18/mol.115.102731.DC1 1521-0111/90/2/80–95$25.00 http://dx.doi.org/10.1124/mol.115.102731 MOLECULAR PHARMACOLOGY Mol Pharmacol 90:80–95, August 2016 Copyright ª 2016 by The American Society for Pharmacology and Experimental Therapeutics Mechanisms of Action of Novel Influenza A/M2 Viroporin Inhibitors Derived from Hexamethylene Amiloride s Pouria H. Jalily, Jodene Eldstrom, Scott C. Miller, Daniel C. Kwan, Sheldon S. -H. Tai, Doug Chou, Masahiro Niikura, Ian Tietjen, and David Fedida Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver (P.H.J., J.E., S.C.M., D.C.K., D.C., I.T., D.F.), and Faculty of Health Sciences, Simon Fraser University, Burnaby (S.S.-H.T., M.N., I.T.), British Columbia, Canada Received December 7, 2015; accepted May 12, 2016 Downloaded from ABSTRACT The increasing prevalence of influenza viruses with resistance to [1,19-biphenyl]-4-carboxylate (27) acts both on adamantane- approved antivirals highlights the need for new anti-influenza sensitive and a resistant M2 variant encoding a serine to asparagine therapeutics. Here we describe the functional properties of hexam- 31 mutation (S31N) with improved efficacy over amantadine and – 5 m m ethylene amiloride (HMA) derived compounds that inhibit the wild- HMA (IC50 0.6 Mand4.4 M, respectively). Whereas 9 inhibited molpharm.aspetjournals.org type and adamantane-resistant forms of the influenza A M2 ion in vitro replication of influenza virus encoding wild-type M2 (EC50 5 channel. -
Chemists Find Binding Site of Protein That Allows Plant Growth 24 September 2013
Chemists find binding site of protein that allows plant growth 24 September 2013 Online Early Edition. Hong and Daniel Cosgrove, professor and holder of the Eberly Chair in Biology at Penn State University, are the lead authors. The research team also includes Tuo Wang, an Iowa State graduate student in chemistry and a graduate assistant for the Ames Laboratory; Linghao Zhong, an associate professor of chemistry at Penn State Mont Alto; Yong Bum Park, a post-doctoral scholar in biology at Penn State; plus Marc Caporini and Melanie Rosay of the Bruker BioSpin Corp. in Billerica, Mass. Three grants from the U.S. Department of Energy supported the research project. This illustration shows the parts of the expansin protein (magenta) that bind to the surface of specific regions of Iowa State's Hong has long used solid-state plant cell walls. Credit: Illustration courtesy of Mei nuclear magnetic resonance (NMR) spectroscopy Hong/Iowa State University. to study structural biology, including the mechanism used by the flu virus to infect host cells. But in this case, that technology wasn't sensitive enough to identify the binding site of the expansin protein. Using a new and super-sensitive instrument, researchers have discovered where a protein binds So the researchers – working with specialists from to plant cell walls, a process that loosens the cell the Bruker BioSpin Corp., a manufacturer of walls and makes it possible for plants to grow. scientific instruments – used a technology called dynamic nuclear polarization (DNP), to enhance the Researchers say the discovery could one day lead sensitivity of spectroscopy instruments. -
Hepatitis C Virus P7—A Viroporin Crucial for Virus Assembly and an Emerging Target for Antiviral Therapy
Viruses 2010, 2, 2078-2095; doi:10.3390/v2092078 OPEN ACCESS viruses ISSN 1999-4915 www.mdpi.com/journal/viruses Review Hepatitis C Virus P7—A Viroporin Crucial for Virus Assembly and an Emerging Target for Antiviral Therapy Eike Steinmann and Thomas Pietschmann * TWINCORE †, Division of Experimental Virology, Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Str. 7, 30625 Hannover, Germany; E-Mail: [email protected] † TWINCORE is a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI). * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +49-511-220027-130; Fax: +49-511-220027-139. Received: 22 July 2010; in revised form: 2 September 2010 / Accepted: 6 September 2010 / Published: 27 September 2010 Abstract: The hepatitis C virus (HCV), a hepatotropic plus-strand RNA virus of the family Flaviviridae, encodes a set of 10 viral proteins. These viral factors act in concert with host proteins to mediate virus entry, and to coordinate RNA replication and virus production. Recent evidence has highlighted the complexity of HCV assembly, which not only involves viral structural proteins but also relies on host factors important for lipoprotein synthesis, and a number of viral assembly co-factors. The latter include the integral membrane protein p7, which oligomerizes and forms cation-selective pores. Based on these properties, p7 was included into the family of viroporins comprising viral proteins from multiple virus families which share the ability to manipulate membrane permeability for ions and to facilitate virus production. Although the precise mechanism as to how p7 and its ion channel function contributes to virus production is still elusive, recent structural and functional studies have revealed a number of intriguing new facets that should guide future efforts to dissect the role and function of p7 in the viral replication cycle. -
A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures
viruses Communication A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures Ryan P. Bennett 1,† , Courtney L. Finch 2,† , Elena N. Postnikova 2 , Ryan A. Stewart 1, Yingyun Cai 2 , Shuiqing Yu 2 , Janie Liang 2, Julie Dyall 2 , Jason D. Salter 1 , Harold C. Smith 1,* and Jens H. Kuhn 2,* 1 OyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USA; [email protected] (R.P.B.); [email protected] (R.A.S.); [email protected] (J.D.S.) 2 NIH/NIAID/DCR/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA; courtney.fi[email protected] (C.L.F.); [email protected] (E.N.P.); [email protected] (Y.C.); [email protected] (S.Y.); [email protected] (J.L.); [email protected] (J.D.) * Correspondence: [email protected] (H.C.S.); [email protected] (J.H.K.); Tel.: +1-585-697-4351 (H.C.S.); +1-301-631-7245 (J.H.K.) † These authors contributed equally to this work. Abstract: Filoviruses, such as Ebola virus and Marburg virus, are of significant human health concern. From 2013 to 2016, Ebola virus caused 11,323 fatalities in Western Africa. Since 2018, two Ebola virus disease outbreaks in the Democratic Republic of the Congo resulted in 2354 fatalities. Although there is progress in medical countermeasure (MCM) development (in particular, vaccines and antibody- based therapeutics), the need for efficacious small-molecule therapeutics remains unmet. Here we describe a novel high-throughput screening assay to identify inhibitors of Ebola virus VP40 matrix protein association with viral particle assembly sites on the interior of the host cell plasma membrane. -
Progressive Multifocal Leukoencephalopathy and the Spectrum of JC Virus-Related Disease
REVIEWS Progressive multifocal leukoencephalopathy and the spectrum of JC virus- related disease Irene Cortese 1 ✉ , Daniel S. Reich 2 and Avindra Nath3 Abstract | Progressive multifocal leukoencephalopathy (PML) is a devastating CNS infection caused by JC virus (JCV), a polyomavirus that commonly establishes persistent, asymptomatic infection in the general population. Emerging evidence that PML can be ameliorated with novel immunotherapeutic approaches calls for reassessment of PML pathophysiology and clinical course. PML results from JCV reactivation in the setting of impaired cellular immunity, and no antiviral therapies are available, so survival depends on reversal of the underlying immunosuppression. Antiretroviral therapies greatly reduce the risk of HIV-related PML, but many modern treatments for cancers, organ transplantation and chronic inflammatory disease cause immunosuppression that can be difficult to reverse. These treatments — most notably natalizumab for multiple sclerosis — have led to a surge of iatrogenic PML. The spectrum of presentations of JCV- related disease has evolved over time and may challenge current diagnostic criteria. Immunotherapeutic interventions, such as use of checkpoint inhibitors and adoptive T cell transfer, have shown promise but caution is needed in the management of immune reconstitution inflammatory syndrome, an exuberant immune response that can contribute to morbidity and death. Many people who survive PML are left with neurological sequelae and some with persistent, low-level viral replication in the CNS. As the number of people who survive PML increases, this lack of viral clearance could create challenges in the subsequent management of some underlying diseases. Progressive multifocal leukoencephalopathy (PML) is for multiple sclerosis. Taken together, HIV, lymphopro- a rare, debilitating and often fatal disease of the CNS liferative disease and multiple sclerosis account for the caused by JC virus (JCV). -
Investigation of Proton Conductance in the Matrix 2 Protein of the Influenza Virus by Solution NMR Spectroscopy © Daniel Turman
Investigation of proton conductance in the matrix 2 protein of the influenza virus by solution NMR spectroscopy © Daniel Turman Emmanuel College Class 0[2012 Abstract The Influenza Matrix 2 (M2) protein is a homo-tetrameric integral membrane protein that forms a proton selective transmembrane channell Its recognized function is to equilibrate pH across the viral envelope following endocytosis and across the trans-golgi membrane during viral maturation2 Its function is vital for viral infection and proliferation but the mechanism and selectivity of proton conductance is not well understood. Mutagenesis studies have identified histidine 37 as the pH sensing element and tryptophan 41 as the gating selectivity filter3 This study uses solution nuclear magnetic resonance spectroscopy and an M2 transmembrane protein construct to elucidate key interactions between the aromatic residues believed to confer proton selectivity and pH dependent conduction of M2 in the low pH open and high pH closed states. PH dependent 13 C_1 H HSQC-Trosy experiments were completed in the pH range of 8.0 - 4.0 and the 13 C, and 13 Co2 chemical shift perturbations of histidine 37 revealed multiple saturation points. The protonation states of histidine 37 suggest a shuttling mechanism for proton conduction. Introduction Influenza is a pathogenic virus that has reached pandemic status four times in the twentieth century. The latest pandemic occurred in 2009 from the influenza A HINI strain (figure 1t The World Health Organization (WHO) commented in July of 2009, "this outbreak is unstoppable." Following this event, significant research has been allocated to understand all aspects of the influenza virus in an effort to produce effective vaccines and medications to prevent and control another pandemic. -
Probing Membrane Protein Structure Using Water Polarization Transfer Solid-State NMR ⇑ Jonathan K
Journal of Magnetic Resonance 247 (2014) 118–127 Contents lists available at ScienceDirect Journal of Magnetic Resonance journal homepage: www.elsevier.com/locate/jmr Perspectives in Magnetic Resonance Probing membrane protein structure using water polarization transfer solid-state NMR ⇑ Jonathan K. Williams, Mei Hong Department of Chemistry, Iowa State University, Ames, IA 50011, United States article info abstract Article history: Water plays an essential role in the structure and function of proteins, lipid membranes and other bio- Received 9 June 2014 logical macromolecules. Solid-state NMR heteronuclear-detected 1H polarization transfer from water Revised 10 August 2014 to biomolecules is a versatile approach for studying water–protein, water–membrane, and water–carbo- Available online 25 August 2014 hydrate interactions in biology. We review radiofrequency pulse sequences for measuring water polari- zation transfer to biomolecules, the mechanisms of polarization transfer, and the application of this Keywords: method to various biological systems. Three polarization transfer mechanisms, chemical exchange, spin Chemical exchange diffusion and NOE, manifest themselves at different temperatures, magic-angle-spinning frequencies, Spin diffusion and pulse irradiations. Chemical exchange is ubiquitous in all systems examined so far, and spin diffusion Ion channels Influenza M2 protein plays the key role in polarization transfer within the macromolecule. Tightly bound water molecules with Heteronuclear correlation long residence times are rare in proteins at ambient temperature. The water polarization-transfer tech- nique has been used to study the hydration of microcrystalline proteins, lipid membranes, and plant cell wall polysaccharides, and to derive atomic-resolution details of the kinetics and mechanism of ion con- duction in channels and pumps. -
Lentivirus and Lentiviral Vectors Fact Sheet
Lentivirus and Lentiviral Vectors Family: Retroviridae Genus: Lentivirus Enveloped Size: ~ 80 - 120 nm in diameter Genome: Two copies of positive-sense ssRNA inside a conical capsid Risk Group: 2 Lentivirus Characteristics Lentivirus (lente-, latin for “slow”) is a group of retroviruses characterized for a long incubation period. They are classified into five serogroups according to the vertebrate hosts they infect: bovine, equine, feline, ovine/caprine and primate. Some examples of lentiviruses are Human (HIV), Simian (SIV) and Feline (FIV) Immunodeficiency Viruses. Lentiviruses can deliver large amounts of genetic information into the DNA of host cells and can integrate in both dividing and non- dividing cells. The viral genome is passed onto daughter cells during division, making it one of the most efficient gene delivery vectors. Most lentiviral vectors are based on the Human Immunodeficiency Virus (HIV), which will be used as a model of lentiviral vector in this fact sheet. Structure of the HIV Virus The structure of HIV is different from that of other retroviruses. HIV is roughly spherical with a diameter of ~120 nm. HIV is composed of two copies of positive ssRNA that code for nine genes enclosed by a conical capsid containing 2,000 copies of the p24 protein. The ssRNA is tightly bound to nucleocapsid proteins, p7, and enzymes needed for the development of the virion: reverse transcriptase (RT), proteases (PR), ribonuclease and integrase (IN). A matrix composed of p17 surrounds the capsid ensuring the integrity of the virion. This, in turn, is surrounded by an envelope composed of two layers of phospholipids taken from the membrane of a human cell when a newly formed virus particle buds from the cell. -
Annual Symposium Program
rd 33 Annual Symposium Program June 30 - July 3, 2019 www.proteinsociety.org Table of Contents 2 Welcome 3 Program Planning Committee Mission 4 Committees The Protein Society is a not-for-profi t scholarly society 7 Corporate Support with a mission to advance state-of-the-art science through international forums that promote commu- 8 Registration nication, cooperation, and collaboration among scientists involved in the study of proteins. 9 Hotel Floor Plan For 33 years, The Protein Society has served as the in- 11 Posters tellectual home of investigators across all disciplines - and from around the world - involved in the study 12 General Information of protein structure, function, and design. The Soci- ety provides forums for scientifi c collaboration and 16 2019 Protein Society Award Winners communication and supports professional growth of young investigators through workshops, networking 22 Travel Awards opportunities, and by encouraging junior research- ers to participate fully in the Annual Symposium. In 24 At-A-Glance addition to our Symposium, the Society’s prestigious journal, Protein Science, serves as an ideal platform 28 Program to further the science of proteins in the broadest sense possible. 42 Exhibitor List and Directory 52 Poster Presentation Schedule 66 Abstracts: TPS Award Winners & Invited Speakers #PS33 90 Posters 1986 - 2019 1 Welcome Program Planning Committee Welcome to Seattle and to the 2019 33rd Annual Sym- posium of the Protein Society! Seattle | June 30 - July 3, 2019 We are excited to bring you this year’s Annual Sym- posium comprising 12 exceptional scientifi c sessions that cover a wide range of scientifi c achievement in the fi eld of protein science, as well as a Nobel Laureate Lecture from 2017 Chemistry Nobel Laure- ate Richard Henderson.