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Structural basis for paramyxovirus-mediated membrane fusion
K A Baker1, R E Dutch, R A Lamb
1Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500, USA.
Abstract:
Paramyxoviruses are responsible for significant human mortality and disease worldwide, but the molecular mechanisms underlying their entry into host cells remain poorly understood. We have solved the crystal structure of a fragment of the simian parainfluenza virus 5 fusion protein (SV5 F), revealing a 96 A long coiled coil surrounded by three antiparallel helices. This structure places the fusion and transmembrane anchor of SV5 F in close proximity with a large intervening domain at the opposite end of the coiled coil. Six amino acids, potentially part of the fusion peptide, form a segment of the central coiled coil, suggesting that this structure extends into the membrane. Deletion mutants of SV5 F indicate that putative flexible tethers between the coiled coil and the viral membrane are dispensable for fusion. The lack of flexible tethers may couple a final conformational change in the F protein directly to the fusion of two bilayers.
Insights
Researchers revealed the structure of simian parainfluenza virus 5 fusion protein (SV5 F). This finding clarifies how paramyxoviruses enter cells, a key step in viral infection and disease.
Area of Science:
- Virology
- Structural Biology
- Molecular Mechanisms
Background:
- Paramyxoviruses cause significant global mortality and disease.
- The molecular mechanisms of paramyxovirus host cell entry are not well understood.
Purpose of the Study:
- To elucidate the structural basis of paramyxovirus entry.
- To understand the role of the fusion protein (F) in viral entry.
Main Methods:
- Crystal structure determination of a simian parainfluenza virus 5 fusion protein (SV5 F) fragment.
- Analysis of the SV5 F structure, including coiled coil and helical arrangements.
- Construction and analysis of deletion mutants of SV5 F.
Main Results:
- The crystal structure revealed a 96 Å long coiled coil surrounded by three antiparallel helices.
- The fusion and transmembrane anchor of SV5 F are positioned near each other.
- Putative flexible tethers between the coiled coil and viral membrane are dispensable for fusion.
Conclusions:
- The structure suggests the coiled coil extends into the membrane, potentially involving fusion peptide elements.
- The dispensability of flexible tethers implies a direct coupling of F protein conformational changes to bilayer fusion.