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

Title: Crystal structure of an orthomyxovirus matrix protein reveals mechanisms for self-polymerization and membrane association

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [2];  [2];  [3];  [2];  [4];  [3];  [2];  [5];  [2]
  1. Rice Univ., Houston, TX (United States); Huazhong Agricultural Univ., Wuhan (People’s Republic of China)
  2. Rice Univ., Houston, TX (United States)
  3. Univ. of Texas Medical School at Houston, TX (United States)
  4. Univ. of Maryland Baltimore County (UMBC), Baltimore, MD (United States)
  5. Huazhong Agricultural Univ., Wuhan (People’s Republic of China)
+ Show Author Affiliations

Many enveloped viruses encode a matrix protein. In the influenza A virus, the matrix protein M1 polymerizes into a rigid protein layer underneath the viral envelope to help enforce the shape and structural integrity of intact viruses. The influenza virus M1 is also known to mediate virus budding as well as the nuclear export of the viral nucleocapsids and their subsequent packaging into nascent viral particles. Despite extensive studies on the influenza A virus M1 (FLUA-M1), only crystal structures of its N-terminal domain are available. Here we report the crystal structure of the full-length M1 from another orthomyxovirus that infects fish, the infectious salmon anemia virus (ISAV). The structure of ISAV-M1 assumes the shape of an elbow, with its N domain closely resembling that of the FLUA-M1. The C domain, which is connected to the N domain through a flexible linker, is made of four α-helices packed as a tight bundle. In the crystal, ISAV-M1 monomers form infinite 2D arrays with a network of interactions involving both the N and C domains. Results from liposome flotation assays indicated that ISAV-M1 binds membrane via electrostatic interactions that are primarily mediated by a positively charged surface loop from the N domain. Furthemore, cryoelectron tomography reconstruction of intact ISA virions identified a matrix protein layer adjacent to the inner leaflet of the viral membrane. The physical dimensions of the virion-associated matrix layer are consistent with the 2D ISAV-M1 crystal lattice, suggesting that the crystal lattice is a valid model for studying M1–M1, M1–membrane, and M1–RNP interactions in the virion.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
Welch Foundation; National Institutes of Health (NIH); National Key Research and Development Program of China; Hamill Foundation; Kresge Science Initiative Endowment Fund
Grant/Contract Number:
C-1565; AU-1714; AI077785; 2016YFD0500205
OSTI ID:
1438909
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, Issue 32; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 16 works
Citation information provided by
Web of Science

References (46)

Characterization of infectious salmon anemia virus, an orthomyxo-like virus isolated from Atlantic salmon (Salmo salar L.). journal January 1997
Infectious salmon anaemia virus nuclear export protein is encoded by a spliced gene product of genomic segment 7 journal October 2013
Spatial structure peculiarities of influenza A virus matrix M1 protein in an acidic solution that simulates the internal lysosomal medium: Influenza virus M1 protein structure journal October 2011
Role of matrix protein in assembling the membrane of vesicular stomatitis virus: reconstitution of matrix protein with negatively charged phospholipid vesicles journal June 1981
RNA-binding properties of influenza A virus matrix protein M1 journal January 1989
The Crystal Structure and RNA-Binding of an Orthomyxovirus Nucleoprotein journal September 2013
Zinc- and pH-Dependent Conformational Transition in a Putative Interdomain Linker Region of the Influenza Virus Matrix Protein M1 † journal February 2003
Infectious salmon anemia virus—Genetics and pathogenesis journal January 2011
Dali server: conservation mapping in 3D journal May 2010
The Influenza Virus M2 Protein Cytoplasmic Tail Interacts with the M1 Protein and Influences Virus Assembly at the Site of Virus Budding journal August 2008
Influenza Virus Matrix Protein Is the Major Driving Force in Virus Budding journal December 2000
Influenza virus assembly and budding journal March 2011
Identification and Characterization of Viral Structural Proteins of Infectious Salmon Anemia Virus journal February 2004
In Vitro Dissection of the Membrane and RNP Binding Activities of Influenza Virus M1 Protein journal March 2001
Formation of Wild-Type and Chimeric Influenza Virus-Like Particles following Simultaneous Expression of Only Four Structural Proteins journal July 2001
Combined Results from Solution Studies on Intact Influenza Virus M1 Protein and from a New Crystal Form of Its N-Terminal Domain Show That M1 Is an Elongated Monomer journal January 2001
Architecture of a nascent viral fusion pore journal February 2010
The polybasic region is not essential for membrane binding of the matrix protein M1 of influenza virus journal January 2009
Structure of a bifunctional membrane-RNA binding protein, influenza virus matrix protein M1 journal March 1997
Segment 8 encodes a structural protein of infectious salmon anaemia virus (ISAV); the co-linear transcript from Segment 7 probably encodes a non-structural or minor structural protein journal January 2002
Effect of M1 protein and low pH on nuclear transport of influenza virus ribonucleoproteins. journal January 1996
pH-dependent conformational changes of a Thogoto virus matrix protein reveal mechanisms of viral assembly and uncoating journal September 2016
The SUMOylation of Matrix Protein M1 Modulates the Assembly and Morphogenesis of Influenza A Virus journal April 2011
Structural organization of a filamentous influenza A virus journal May 2010
The in situ spatial arrangement of the influenza A virus matrix protein M1 assessed by tritium bombardment journal July 1999
Programmed cell clearance: From nematodes to humans journal January 2017
The Crystal Structure of the Influenza Matrix Protein M1 at Neutral pH: M1–M1 Protein Interfaces Can Rotate in the Oligomeric Structures of M1 journal October 2001
Influenza A virus NS2 protein mediates vRNP nuclear export through NES-independent interaction with hCRM1 journal December 2000
Conservation of the influenza virus membrane protein (M1) amino acid sequence and an open reading frame of RNA segment 7 encoding a second protein (M2) in H1N1 and H3N2 strains journal July 1981
Identification of the domains of the influenza A virus M1 matrix protein required for NP binding, oligomerization and incorporation into virions journal August 2007
Membrane Interaction of Influenza Virus M1 Protein journal February 2000
The Matrix protein M1 from influenza C virus induces tubular membrane invaginations in an in vitro cell membrane model journal January 2017
Role of influenza virus M1 protein in the viral budding process journal October 2001
Molecular architecture of native HIV-1 gp120 trimers journal July 2008
Lysine Methylation as a Routine Rescue Strategy for Protein Crystallization journal November 2006
At Low pH, Influenza Virus Matrix Protein M1 Undergoes a Conformational Change Prior to Dissociating from the Membrane journal March 2013
Association of Influenza Virus Matrix Protein with Ribonucleoproteins journal September 1999
Mechanism for inhibition of influenza virus RNA polymerase activity by matrix protein. journal January 1996
Structural Analysis of Influenza A Virus Matrix Protein M1 and Its Self-Assemblies at Low pH journal December 2013
Influenza Virus Hemagglutinin and Neuraminidase, but Not the Matrix Protein, Are Required for Assembly and Budding of Plasmid-Derived Virus-Like Particles journal May 2007
Functional and antigenic domains of the matrix (M1) protein of influenza A virus. journal January 1987
Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2) journal September 2003
Influenza virus M1 protein binds to RNA through its nuclear localization signal. journal July 1997
Crystal Structures of Influenza A Virus Matrix Protein M1: Variations on a Theme journal October 2014
Analysis of host- and strain-dependent cell death responses during infectious salmon anemia virus infection in vitro journal January 2009
Electrostatic Architecture of the Infectious Salmon Anemia Virus (ISAV) Core Fusion Protein Illustrates a Carboxyl-Carboxylate pH Sensor journal June 2015

Cited By (9)

Promotion of virus assembly and organization by the measles virus matrix protein journal April 2018
Influenza virus Matrix Protein M1 preserves its conformation with pH, changing multimerization state at the priming stage due to electrostatics journal December 2017
Maintaining pH-dependent conformational flexibility of M1 is critical for efficient influenza A virus replication journal January 2017
Deep Mutational Scan of the Highly Conserved Influenza A Virus M1 Matrix Protein Reveals Substantial Intrinsic Mutational Tolerance journal April 2019
Continuing evolution of H6N2 influenza a virus in South African chickens and the implications for diagnosis and control journal December 2019
The Role of Matrix Protein 2 Ectodomain in the Development of Universal Influenza Vaccines journal April 2019
Matrix proteins of enveloped viruses: a case study of Influenza A virus M1 protein journal February 2018
Influenza virus Matrix Protein M1 preserves its conformation with pH, changing multimerization state at the priming stage due to electrostatics text January 2017
Infectious salmon anaemia virus—molecular biology and pathogenesis of the infection journal January 2020

Similar Records

Structure of the infectious salmon anemia virus receptor complex illustrates a unique binding strategy for attachment
Journal Article · Mon Mar 20 00:00:00 EDT 2017 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1438909
Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity
Journal Article · Sun May 15 00:00:00 EDT 2016 · Virology · OSTI ID:1438909
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:1438909
+6 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
matrix protein
structure
orthomyoxovirus
ISAV
assembly