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Published on: March 24, 2017
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.
Abstract:
The matrix protein (M) of respiratory syncytial virus (RSV), the prototype viral member of the Pneumovirinae (family Paramyxoviridae, order Mononegavirales), has been crystallized and the structure determined to a resolution of 1.6 A. The structure comprises 2 compact beta-rich domains connected by a relatively unstructured linker region. Due to the high degree of side-chain order in the structure, an extensive contiguous area of positive surface charge covering approximately 600 A(2) can be resolved. This unusually large patch of positive surface potential spans both domains and the linker, and provides a mechanism for driving the interaction of the protein with a negatively-charged membrane surface or other virion components such as the nucleocapsid. This patch is complemented by regions of high hydrophobicity and a striking planar arrangement of tyrosine residues encircling the C-terminal domain. Comparison of the RSV M sequence with other members of the Pneumovirinae shows that regions of divergence correspond to surface exposed loops in the M structure, with the majority of viral species-specific differences occurring in the N-terminal domain.
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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