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Basic Characteristics of Mutations
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Mutation Site
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A82V |
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Mutation Site Sentence
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Molecular basis for the increased fusion activity of the Ebola virus glycoprotein epidemic variant A82V: Insights from simulations and experiments |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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GP |
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Standardized Encoding Gene
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GP
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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NPC1
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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40186866
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Title
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Molecular basis for the increased fusion activity of the Ebola virus glycoprotein epidemic variant A82V: Insights from simulations and experiments
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Author
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Durham ND,Jain A,Howard A,Luban J,Munro JB
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Journal
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Cell reports
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Journal Info
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2025 Apr 22;44(4):115521
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Abstract
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During the 2013-2016 Ebola virus (EBOV) epidemic in Western Africa, an A82V mutation emerged in the envelope glycoprotein (GP) that persisted in most circulating isolates. Previous studies demonstrated that A82V increased GP-mediated membrane fusion and altered its dependence on host factors. The mechanistic basis for these observations, in particular the impact of A82V on the conformational changes in GP that are needed for membrane fusion, has not been evaluated in molecular detail. Here, using molecular dynamics simulations, fluorescence correlation spectroscopy, and single-molecule Forster resonance energy transfer imaging, we specify the molecular mechanism by which A82V alters GP conformation to enhance viral entry. In so doing, we identify an allosteric network of interactions that links the receptor-binding site to the fusion loop of GP. Thus, the naturally occurring A82V mutation can tune the conformational dynamics of EBOV GP to enhance fusion loop mobility and subsequent viral fusion and infectivity in human cells.
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Sequence Data
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-
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