U.S. Department of EnergyOffice of Scientific and Technical Information
Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression
Abstract
Marburg virus (MARV), a member of the filovirus family, causes severe hemorrhagic fever with up to 90% lethality. MARV matrix protein VP40 is essential for assembly and release of newly copied viruses and also suppresses immune signaling in the infected cell. Here we report the crystal structure of MARV VP40. We found that MARV VP40 forms a dimer in solution, mediated by N-terminal domains, and that formation of this dimer is essential for budding of virus-like particles. We also found the N-terminal domain to be necessary and sufficient for immune antagonism. The C-terminal domains of MARV VP40 are dispensable for immunosuppression but are required for virus assembly. The C-terminal domains are only 16% identical to those of Ebola virus, differ in structure from those of Ebola virus, and form a distinct broad and flat cationic surface that likely interacts with the cell membrane during virus assembly. Marburg virus, a cousin of Ebola virus, causes severe hemorrhagic fever, with up to 90% lethality seen in recent outbreaks. Molecular structures and visual images of the proteins of Marburg virus are essential for the development of antiviral drugs. One key protein in the Marburg virus life cycle is VP40, which both assembles themore »
- Authors:
-
- The Scripps Research Inst., La Jolla, CA (United States)
- Univ. of Tokyo (Japan)
- Univ. of Notre Dame, IN (United States)
- Univ. of Wisconsin, Madison, WI (United States)
- Univ. of Notre Dame, IN (United States); Indiana Univ. School of Medicine, South Bend, IN (United States)
- Univ. of Tokyo (Japan); Univ. of Wisconsin, Madison, WI (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; Japan Society for Promotion of Science; Health and Labor Sciences Research; HHS; National Institutes of Health (NIH); National Inst. of Allergy and Infectious Diseases (NIAID); National Inst. of General Medical Sciences (NIGMS); Burroughs Wellcome Fund (BWF)
- OSTI Identifier:
- 1252764
- Grant/Contract Number:
- AC02-06CH11357; AI081077; R44AI08843; T32GM075762
- Resource Type:
- Journal Article: Accepted Manuscript
- Journal Name:
- Journal of Virology
- Additional Journal Information:
- Journal Volume: 90; Journal Issue: 4; Journal ID: ISSN 0022-538X
- Publisher:
- American Society for Microbiology
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Oda, Shun-ichiro, Noda, Takeshi, Wijesinghe, Kaveesha J., Halfmann, Peter, Bornholdt, Zachary A., Abelson, Dafna M., Armbrust, Tammy, Stahelin, Robert V., Kawaoka, Yoshihiro, and Saphire, Erica Ollmann. Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression. United States: N. p., 2016.
Web. doi:10.1128/JVI.01597-15.
Oda, Shun-ichiro, Noda, Takeshi, Wijesinghe, Kaveesha J., Halfmann, Peter, Bornholdt, Zachary A., Abelson, Dafna M., Armbrust, Tammy, Stahelin, Robert V., Kawaoka, Yoshihiro, & Saphire, Erica Ollmann. Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression. United States. https://doi.org/10.1128/JVI.01597-15
Oda, Shun-ichiro, Noda, Takeshi, Wijesinghe, Kaveesha J., Halfmann, Peter, Bornholdt, Zachary A., Abelson, Dafna M., Armbrust, Tammy, Stahelin, Robert V., Kawaoka, Yoshihiro, and Saphire, Erica Ollmann. 2016.
"Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression". United States. https://doi.org/10.1128/JVI.01597-15. https://www.osti.gov/servlets/purl/1252764.
@article{osti_1252764,
title = {Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression},
author = {Oda, Shun-ichiro and Noda, Takeshi and Wijesinghe, Kaveesha J. and Halfmann, Peter and Bornholdt, Zachary A. and Abelson, Dafna M. and Armbrust, Tammy and Stahelin, Robert V. and Kawaoka, Yoshihiro and Saphire, Erica Ollmann},
abstractNote = {Marburg virus (MARV), a member of the filovirus family, causes severe hemorrhagic fever with up to 90% lethality. MARV matrix protein VP40 is essential for assembly and release of newly copied viruses and also suppresses immune signaling in the infected cell. Here we report the crystal structure of MARV VP40. We found that MARV VP40 forms a dimer in solution, mediated by N-terminal domains, and that formation of this dimer is essential for budding of virus-like particles. We also found the N-terminal domain to be necessary and sufficient for immune antagonism. The C-terminal domains of MARV VP40 are dispensable for immunosuppression but are required for virus assembly. The C-terminal domains are only 16% identical to those of Ebola virus, differ in structure from those of Ebola virus, and form a distinct broad and flat cationic surface that likely interacts with the cell membrane during virus assembly. Marburg virus, a cousin of Ebola virus, causes severe hemorrhagic fever, with up to 90% lethality seen in recent outbreaks. Molecular structures and visual images of the proteins of Marburg virus are essential for the development of antiviral drugs. One key protein in the Marburg virus life cycle is VP40, which both assembles the virus and suppresses the immune system. Furthermore, we provide the molecular structure of Marburg virus VP40, illustrate differences from VP40 of Ebola virus, and reveal surfaces by which Marburg VP40 assembles progeny and suppresses immune function.},
doi = {10.1128/JVI.01597-15},
url = {https://www.osti.gov/biblio/1252764},
journal = {Journal of Virology},
issn = {0022-538X},
number = 4,
volume = 90,
place = {United States},
year = {Thu Jan 28 00:00:00 EST 2016},
month = {Thu Jan 28 00:00:00 EST 2016}
}
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Works referenced in this record:
Oligomerization and polymerization of the filovirus matrix protein VP40
journal, August 2003
- Timmins, Joanna; Schoehn, Guy; Kohlhaas, Christine
- Virology, Vol. 312, Issue 2
The spatio-temporal distribution dynamics of Ebola virus proteins and RNA in infected cells
journal, February 2013
- Nanbo, Asuka; Watanabe, Shinji; Halfmann, Peter
- Scientific Reports, Vol. 3, Issue 1
The Buccaneer software for automated model building. 1. Tracing protein chains
journal, August 2006
- Cowtan, Kevin
- Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 9
Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain–like mechanism
journal, March 2007
- Mattila, Pieta K.; Pykäläinen, Anette; Saarikangas, Juha
- Journal of Cell Biology, Vol. 176, Issue 7
Electrostatics of nanosystems: Application to microtubules and the ribosome
journal, August 2001
- Baker, N. A.; Sept, D.; Joseph, S.
- Proceedings of the National Academy of Sciences, Vol. 98, Issue 18, p. 10037-10041
The Matrix Protein of Marburg Virus Is Transported to the Plasma Membrane along Cellular Membranes: Exploiting the Retrograde Late Endosomal Pathway
journal, February 2004
- Kolesnikova, L.; Bamberg, S.; Berghofer, B.
- Journal of Virology, Vol. 78, Issue 5
Substructure solution with SHELXD
journal, September 2002
- Schneider, Thomas R.; Sheldrick, George M.
- Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 10
VP40, the Matrix Protein of Marburg Virus, Is Associated with Membranes of the Late Endosomal Compartment
journal, February 2002
- Kolesnikova, L.; Bugany, H.; Klenk, H. -D.
- Journal of Virology, Vol. 76, Issue 4
Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties
journal, February 2009
- Neumann, P.; Lieber, D.; Meyer, S.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 10
Surface features of a Mononegavirales matrix protein indicate sites of membrane interaction
journal, February 2009
- Money, V. A.; McPhee, H. K.; Mosely, J. A.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 11
Ebola Virus VP40-Induced Particle Formation and Association with the Lipid Bilayer
journal, June 2001
- Jasenosky, L. D.; Neumann, G.; Lukashevich, I.
- Journal of Virology, Vol. 75, Issue 11
ABS : a program to determine absolute configuration and evaluate anomalous scatterer substructure
journal, May 2004
- Hao, Quan
- Journal of Applied Crystallography, Vol. 37, Issue 3
Coot model-building tools for molecular graphics
journal, November 2004
- Emsley, Paul; Cowtan, Kevin
- Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
Assembly of the Marburg virus envelope: Marburg virus assembly
journal, December 2012
- Mittler, Eva; Kolesnikova, Larissa; Herwig, Astrid
- Cellular Microbiology, Vol. 15, Issue 2
Pathogenesis of Marburg Hemorrhagic Fever in Cynomolgus Macaques
journal, November 2011
- Hensley, Lisa E.; Alves, Derron A.; Geisbert, Joan B.
- The Journal of Infectious Diseases, Vol. 204, Issue suppl_3
Ebola Virus VP24 Targets a Unique NLS Binding Site on Karyopherin Alpha 5 to Selectively Compete with Nuclear Import of Phosphorylated STAT1
journal, August 2014
- Xu, Wei; Edwards, Megan R.; Borek, Dominika M.
- Cell Host & Microbe, Vol. 16, Issue 2
Maximum-likelihood density modification
journal, August 2000
- Terwilliger, Thomas C.
- Acta Crystallographica Section D Biological Crystallography, Vol. 56, Issue 8
Auto-Rickshaw : an automated crystal structure determination platform as an efficient tool for the validation of an X-ray diffraction experiment
journal, March 2005
- Panjikar, Santosh; Parthasarathy, Venkataraman; Lamzin, Victor S.
- Acta Crystallographica Section D Biological Crystallography, Vol. 61, Issue 4
Generation of Marburg virus-like particles by co-expression of glycoprotein and matrix protein
journal, January 2004
- Swenson, Dana L.; Warfield, Kelly L.; Kuehl, Kathleen
- FEMS Immunology & Medical Microbiology, Vol. 40, Issue 1
Effect of Ebola virus proteins GP, NP and VP35 on VP40 VLP morphology
journal, May 2006
- Johnson, Reed F.; Bell, Peter; Harty, Ronald N.
- Virology Journal, Vol. 3
Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope
journal, January 1964
- Bangham, A. D.; Horne, R. W.
- Journal of Molecular Biology, Vol. 8, Issue 5
The Matrix Protein VP40 from Ebola Virus Octamerizes into Pore-like Structures with Specific RNA Binding Properties
journal, April 2003
- Gomis-Rüth, F. Xavier; Dessen, Andréa; Timmins, Joanna
- Structure, Vol. 11, Issue 4
ESPript/ENDscript: extracting and rendering sequence and 3D information from atomic structures of proteins
journal, July 2003
- Gouet, P.
- Nucleic Acids Research, Vol. 31, Issue 13
Structural Rearrangement of Ebola Virus VP40 Begets Multiple Functions in the Virus Life Cycle
journal, August 2013
- Bornholdt, Zachary A.; Noda, Takeshi; Abelson, Dafna M.
- Cell, Vol. 154, Issue 4
Marburg Virus Evades Interferon Responses by a Mechanism Distinct from Ebola Virus
journal, January 2010
- Valmas, Charalampos; Grosch, Melanie N.; Schümann, Michael
- PLoS Pathogens, Vol. 6, Issue 1
Experimental phasing with SHELXC / D / E : combining chain tracing with density modification
journal, March 2010
- Sheldrick, George M.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
Forty-Five Years of Marburg Virus Research
journal, October 2012
- Brauburger, Kristina; Hume, Adam J.; Mühlberger, Elke
- Viruses, Vol. 4, Issue 10
The CCP4 suite programs for protein crystallography
journal, September 1994
- ,
- Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 5, p. 760-763
Identification of Amino Acids in Marburg Virus VP40 That Are Important for Virus-Like Particle Budding
journal, November 2011
- Makino, Akiko; Yamayoshi, Seiya; Shinya, Kyoko
- The Journal of Infectious Diseases, Vol. 204, Issue suppl_3
T-coffee: a novel method for fast and accurate multiple sequence alignment 1 1Edited by J. Thornton
journal, September 2000
- Notredame, Cédric; Higgins, Desmond G.; Heringa, Jaap
- Journal of Molecular Biology, Vol. 302, Issue 1
Novel methods for liposome preparation
journal, January 2014
- Patil, Yogita P.; Jadhav, Sameer
- Chemistry and Physics of Lipids, Vol. 177
[20] Processing of X-ray diffraction data collected in oscillation mode
book, January 1997
- Otwinowski, Zbyszek; Minor, Wladek
- Macromolecular Crystallography Part A, 307-326
Breaking good resolutions with ARP/wARP
journal, November 2003
- Morris, Richard J.; Zwart, Petrus H.; Cohen, Serge
- Journal of Synchrotron Radiation, Vol. 11, Issue 1
Phospholipid model membranes. II. Permeability properties of hydrated liquid crystals
journal, September 1967
- Papahadjopoulos, Demetrios; Watkins, J. C.
- Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 135, Issue 4
Molecular Mechanisms of Membrane Deformation by I-BAR Domain Proteins
journal, January 2009
- Saarikangas, Juha; Zhao, Hongxia; Pykäläinen, Anette
- Current Biology, Vol. 19, Issue 2
Works referencing / citing this record:
A cationic, C-terminal patch and structural rearrangements in Ebola virus matrix VP40 protein control its interactions with phosphatidylserine
journal, January 2018
- Del Vecchio, Kathryn; Frick, Cary T.; Gc, Jeevan B.
- Journal of Biological Chemistry, Vol. 293, Issue 9
Matrix proteins of enveloped viruses: a case study of Influenza A virus M1 protein
journal, February 2018
- Kordyukova, Larisa V.; Shtykova, Eleonora V.; Baratova, Lyudmila A.
- Journal of Biomolecular Structure and Dynamics, Vol. 37, Issue 3
Structural exploration of viral matrix protein 40 interaction with the transition metal ions (Ag + and Cu 2+ )
journal, November 2018
- Saranya, V.; Shankar, R.; Vijayakumar, S.
- Journal of Biomolecular Structure and Dynamics, Vol. 37, Issue 11
Recent advances in marburgvirus research
journal, January 2019
- Olejnik, Judith; Mühlberger, Elke; Hume, Adam J.
- F1000Research, Vol. 8
Unveiling a Drift Resistant Cryptotope within Marburgvirus Nucleoprotein Recognized by Llama Single-Domain Antibodies
journal, October 2017
- Garza, John Anthony; Taylor, Alexander Bryan; Sherwood, Laura Jo
- Frontiers in Immunology, Vol. 8
Host and Viral Proteins Modulating Ebola and Marburg Virus Egress
journal, January 2019
- Gordon, Tamsin B.; Hayward, Joshua A.; Marsh, Glenn A.
- Viruses, Vol. 11, Issue 1