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Sequential conformational rearrangements in flavivirus membrane fusion.


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.

SUBMITTER: Chao LH 

PROVIDER: S-EPMC4293572 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Sequential conformational rearrangements in flavivirus membrane fusion.

Chao Luke H LH   Klein Daryl E DE   Schmidt Aaron G AG   Peña Jennifer M JM   Harrison Stephen C SC  

eLife 20141205


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 p  ...[more]

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