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

Wenting Zhang1,2, Wenjie Zheng1, Yukimatsu Toh1

  • 1Department of BioSciences, Rice University, Houston, TX 77251.

Proceedings of the National Academy of Sciences of the United States of America
|July 26, 2017
PubMed

Insights

The crystal structure of infectious salmon anemia virus matrix protein (ISAV-M1) reveals an elbow shape and 2D arrays, providing a model for viral structure and assembly. This research advances understanding of matrix protein functions in enveloped viruses.

Area of Science:

  • Virology
  • Structural Biology
  • Biochemistry

Background:

  • Enveloped viruses utilize matrix proteins for structural integrity and assembly.
  • Influenza A virus matrix protein (FLUA-M1) functions are well-studied, but only its N-terminal domain structure is known.
  • Infectious salmon anemia virus (ISAV) is an important fish pathogen within the Orthomyxoviridae family.

Purpose of the Study:

  • To determine the full-length crystal structure of the ISAV matrix protein (ISAV-M1).
  • To investigate the interactions of ISAV-M1 with membranes and its potential role in viral assembly.
  • To establish a structural model for understanding matrix protein functions in enveloped viruses.

Main Methods:

  • X-ray crystallography to determine the full-length ISAV-M1 structure.
  • Liposome flotation assays to study ISAV-M1 membrane binding.
  • Cryoelectron tomography to visualize the matrix protein layer in intact ISAV virions.

Main Results:

  • The ISAV-M1 structure exhibits an elbow conformation with N and C domains linked flexibly.
  • ISAV-M1 monomers form 2D arrays in crystals, suggesting a potential assembly mechanism.
  • ISAV-M1 binds to membranes via electrostatic interactions mediated by a positively charged N-terminal loop.
  • Cryo-ET confirmed a matrix protein layer in ISAV virions consistent with the crystal lattice model.

Conclusions:

  • The 2D crystal lattice of ISAV-M1 serves as a valid model for studying M1-M1, M1-membrane, and M1-RNP interactions.
  • Understanding ISAV-M1 structure and interactions provides insights into matrix protein roles in enveloped virus assembly and structural biology.
  • This study offers a structural basis for further research into Orthomyxoviridae matrix proteins and potential antiviral strategies.
Keywords:
ISAVassemblymatrix proteinorthomyoxovirusstructure

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