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Elife. 2014 Dec 5;3:e04389. doi: 10.7554/eLife.04389.

Sequential conformational rearrangements in flavivirus membrane fusion.

Author information

1
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States.

Abstract

The West Nile Virus (WNV) envelope protein, E, promotes membrane fusion during viral cell entry by undergoing a low-pH triggered conformational reorganization. We have examined the mechanism of WNV fusion and sought evidence for potential intermediates during the conformational transition by following hemifusion of WNV virus-like particles (VLPs) in a single particle format. We have introduced specific mutations into E, to relate their influence on fusion kinetics to structural features of the protein. At the level of individual E subunits, trimer formation and membrane engagement of the threefold clustered fusion loops are rate-limiting. Hemifusion requires at least two adjacent trimers. Simulation of the kinetics indicates that availability of competent monomers within the contact zone between virus and target membrane makes trimerization a bottleneck in hemifusion. We discuss the implications of the model we have derived for mechanisms of membrane fusion in other contexts.

KEYWORDS:

West Nile virus; biophysics; conformational change; flavivirus; kinetics; membrane fusion; single particle; structural biology; viruses

PMID:
25479384
PMCID:
PMC4293572
DOI:
10.7554/eLife.04389
[Indexed for MEDLINE]
Free PMC Article

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