Assembly of Ebola Virus Matrix Protein VP40 Is Regulated by Latch-Like Properties of N and C Terminal Tails

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dc.contributor.authorSilva, Leslie P.
dc.contributor.authorVanzile, Michael
dc.contributor.authorBavari, Sina
dc.contributor.authorAman, J. M. Javad
dc.contributor.authorSchriemer, David C.
dc.date.accessioned2017-06-01T19:57:24Z
dc.date.available2017-06-01T19:57:24Z
dc.date.issued2012-7-5
dc.description.abstractThe matrix protein VP40 coordinates numerous functions in the viral life cycle of the Ebola virus. These range from the regulation of viral transcription to morphogenesis, packaging and budding of mature virions. Similar to the matrix proteins of other nonsegmented, negative-strand RNA viruses, VP40 proceeds through intermediate states of assembly (e.g. octamers) but it remains unclear how these intermediates are coordinated with the various stages of the life cycle. In this study, we investigate the molecular basis of synchronization as governed by VP40. Hydrogen/deuterium exchange mass spectrometry was used to follow induced structural and conformational changes in VP40. Together with computational modeling, we demonstrate that both extreme N and C terminal tail regions stabilize the monomeric state through a direct association. The tails appear to function as a latch, released upon a specific molecular trigger such as RNA ligation. We propose that triggered release of the tails permits the coordination of late-stage events in the viral life cycle, at the inner membrane of the host cell. Specifically, N-tail release exposes the L-domain motifs PTAP/PPEY to the transport and budding complexes, whereas triggered C-tail release could improve association with the site of budding.en_US
dc.description.refereedYes
dc.description.sponsorshipThe work was supported in part by grants from Alberta Innovates - Health Solutions, the Defense Threat Reduction Agency [JSTO-CBD project 44.10022-08-RD-B and TMTI (Transformational Medical Technologies Initiative) project 0048-09-RD-T]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.identifier.citationSilva LP, Vanzile M, Bavari S, Aman JMJ, Schriemer DC (2012) Assembly of Ebola Virus Matrix Protein VP40 Is Regulated by Latch-Like Properties of N and C Terminal Tails. PLoS ONE 7(7): e39978. https://doi.org/10.1371/journal.pone.0039978en_US
dc.identifier.doi10.1371/journal.pone.0039978
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/33776
dc.identifier.grantnumberJSTO-CBD project 44.10022-08-RD-B
dc.identifier.grantnumberTMTI0048-09-RD-T
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/1880/52007
dc.language.isoenen_US
dc.publisherPLOS One
dc.publisher.departmentBiochemistry and Moleculary Biology
dc.publisher.facultyCumming School of Medicine
dc.publisher.institutionUniversity of Calgaryen_US
dc.publisher.urlhttp://journals.plos.org/plosone/en_US
dc.subjectUrea
dc.subjectRNA denaturation
dc.subjectEbola virus
dc.subjectPeptide mapping
dc.subjectCell membranes
dc.subjectLife cycles
dc.subjectMembrane proteins
dc.subjectSequence motif analysis
dc.titleAssembly of Ebola Virus Matrix Protein VP40 Is Regulated by Latch-Like Properties of N and C Terminal Tails
dc.typejournal article
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