Surface features of a Mononegavirales matrix protein indicate sites of membrane interaction

Victoria A Money1, Helen K McPhee, Jackie A Mosely

  • 1The Maurice Wilkins Centre for Molecular Biodiscovery and the School of Biological Sciences, University of Auckland, Thomas Building, 3a Symonds Street, Auckland Central 1010, New Zealand.

Insights

The crystal structure of respiratory syncytial virus (RSV) matrix protein reveals a large positive surface charge patch. This finding explains how RSV M protein interacts with viral membranes and nucleocapsids.

Area of Science:

  • Structural biology
  • Virology
  • Molecular biology

Background:

  • Respiratory syncytial virus (RSV) is a major human pathogen.
  • The matrix (M) protein is essential for RSV virion assembly.
  • Understanding RSV M protein structure is key to developing antivirals.

Purpose of the Study:

  • To determine the high-resolution crystal structure of the RSV matrix (M) protein.
  • To elucidate the structural basis for M protein interactions within the virion.

Main Methods:

  • X-ray crystallography
  • Structure determination to 1.6 A resolution
  • Surface charge and hydrophobicity analysis

Main Results:

  • The RSV M protein structure consists of two beta-rich domains linked by an unstructured region.
  • A large (approx. 600 A2) contiguous positive surface charge patch was identified.
  • Hydrophobic regions and a planar arrangement of tyrosine residues were observed.
  • Sequence comparison revealed species-specific differences in surface-exposed loops, primarily in the N-terminal domain.

Conclusions:

  • The identified positive surface charge patch likely mediates interactions with negatively charged viral membranes and nucleocapsids.
  • Structural variations in surface loops may contribute to RSV M protein's role in viral assembly and host interactions.
  • The structure provides a basis for understanding M protein function and for designing targeted therapeutics.

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