skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Journal Article · · Journal of Virology
DOI:https://doi.org/10.1128/JVI.01597-15· OSTI ID:1252764
 [1];  [2];  [3];  [4];  [1];  [1];  [4];  [5];  [6];  [1]
  1. The Scripps Research Inst., La Jolla, CA (United States)
  2. Univ. of Tokyo (Japan)
  3. Univ. of Notre Dame, IN (United States)
  4. Univ. of Wisconsin, Madison, WI (United States)
  5. Univ. of Notre Dame, IN (United States); Indiana Univ. School of Medicine, South Bend, IN (United States)
  6. Univ. of Tokyo (Japan); Univ. of Wisconsin, Madison, WI (United States)
+ Show Author Affiliations

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
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)
Grant/Contract Number:
AC02-06CH11357; AI081077; R44AI08843; T32GM075762
OSTI ID:
1252764
Journal Information:
Journal of Virology, Vol. 90, Issue 4; ISSN 0022-538X
Publisher:
American Society for MicrobiologyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 27 works
Citation information provided by
Web of Science

References (36)

Oligomerization and polymerization of the filovirus matrix protein VP40 journal August 2003
The spatio-temporal distribution dynamics of Ebola virus proteins and RNA in infected cells journal February 2013
The Buccaneer software for automated model building. 1. Tracing protein chains journal August 2006
Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain–like mechanism journal March 2007
Electrostatics of nanosystems: Application to microtubules and the ribosome journal August 2001
The Matrix Protein of Marburg Virus Is Transported to the Plasma Membrane along Cellular Membranes: Exploiting the Retrograde Late Endosomal Pathway journal February 2004
Substructure solution with SHELXD journal September 2002
VP40, the Matrix Protein of Marburg Virus, Is Associated with Membranes of the Late Endosomal Compartment journal February 2002
Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties journal February 2009
Surface features of a Mononegavirales matrix protein indicate sites of membrane interaction journal February 2009
Ebola Virus VP40-Induced Particle Formation and Association with the Lipid Bilayer journal June 2001
ABS : a program to determine absolute configuration and evaluate anomalous scatterer substructure journal May 2004
Coot model-building tools for molecular graphics journal November 2004
Transient Mammalian Cell Transfection with Polyethylenimine (PEI) book January 2013
Assembly of the Marburg virus envelope: Marburg virus assembly journal December 2012
Pathogenesis of Marburg Hemorrhagic Fever in Cynomolgus Macaques journal November 2011
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
Maximum-likelihood density modification journal August 2000
Auto-Rickshaw : an automated crystal structure determination platform as an efficient tool for the validation of an X-ray diffraction experiment journal March 2005
Generation of Marburg virus-like particles by co-expression of glycoprotein and matrix protein journal January 2004
Effect of Ebola virus proteins GP, NP and VP35 on VP40 VLP morphology journal May 2006
Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope journal January 1964
The Matrix Protein VP40 from Ebola Virus Octamerizes into Pore-like Structures with Specific RNA Binding Properties journal April 2003
ESPript/ENDscript: extracting and rendering sequence and 3D information from atomic structures of proteins journal July 2003
Structural Rearrangement of Ebola Virus VP40 Begets Multiple Functions in the Virus Life Cycle journal August 2013
Marburg Virus Evades Interferon Responses by a Mechanism Distinct from Ebola Virus journal January 2010
Experimental phasing with SHELXC / D / E : combining chain tracing with density modification journal March 2010
Forty-Five Years of Marburg Virus Research journal October 2012
The CCP4 suite programs for protein crystallography journal September 1994
Identification of Amino Acids in Marburg Virus VP40 That Are Important for Virus-Like Particle Budding journal November 2011
T-coffee: a novel method for fast and accurate multiple sequence alignment 1 1Edited by J. Thornton journal September 2000
Novel methods for liposome preparation journal January 2014
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997
Breaking good resolutions with ARP/wARP journal November 2003
Phospholipid model membranes. II. Permeability properties of hydrated liquid crystals journal September 1967
Molecular Mechanisms of Membrane Deformation by I-BAR Domain Proteins journal January 2009

Cited By (6)

A cationic, C-terminal patch and structural rearrangements in Ebola virus matrix VP40 protein control its interactions with phosphatidylserine journal January 2018
Matrix proteins of enveloped viruses: a case study of Influenza A virus M1 protein journal February 2018
Structural exploration of viral matrix protein 40 interaction with the transition metal ions (Ag + and Cu 2+ ) journal November 2018
Recent advances in marburgvirus research journal January 2019
Unveiling a Drift Resistant Cryptotope within Marburgvirus Nucleoprotein Recognized by Llama Single-Domain Antibodies journal October 2017
Host and Viral Proteins Modulating Ebola and Marburg Virus Egress journal January 2019

Similar Records

Crystal Structure of the Marburg Virus VP35 Oligomerization Domain
Journal Article · Wed Nov 09 00:00:00 EST 2016 · Journal of Virology · OSTI ID:1252764
+5 more
Ebola and Marburg virus matrix layers are locally ordered assemblies of VP40 dimers
Journal Article · Mon Oct 05 00:00:00 EDT 2020 · eLife · OSTI ID:1252764
+6 more
Dimerization Controls Marburg Virus VP24-dependent Modulation of Host Antioxidative Stress Responses
Journal Article · Thu Aug 04 00:00:00 EDT 2016 · Journal of Molecular Biology · OSTI ID:1252764
+7 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES