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dc.contributor.authorKong, Leopolden_US
dc.contributor.authorHe, Linlingen_US
dc.contributor.authorde Val, Nataliaen_US
dc.contributor.authorVora, Nemilen_US
dc.contributor.authorMorris, Charles D.en_US
dc.contributor.authorAzadnia, Parisaen_US
dc.contributor.authorSok, Devinen_US
dc.contributor.authorZhou, Binen_US
dc.contributor.authorBurton, Dennis R.en_US
dc.contributor.authorWard, Andrew B.en_US
dc.contributor.authorWilson, Ian A.en_US
dc.contributor.authorZhu, Jiangen_US
dc.date.accessioned2016-08-09T14:52:23Z
dc.date.issued2016en_US
dc.identifier.citationKong, L., L. He, N. de Val, N. Vora, C. D. Morris, P. Azadnia, D. Sok, et al. 2016. “Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability.” Nature Communications 7 (1): 12040. doi:10.1038/ncomms12040. http://dx.doi.org/10.1038/ncomms12040.en
dc.identifier.issn2041-1723en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:27822121
dc.description.abstractThe trimeric HIV-1 envelope glycoprotein (Env) is critical for host immune recognition and neutralization. Despite advances in trimer design, the roots of Env trimer metastability remain elusive. Here we investigate the contribution of two Env regions to metastability. First, we computationally redesign a largely disordered bend in heptad region 1 (HR1) of SOSIP trimers that connects the long, central HR1 helix to the fusion peptide, substantially improving the yield of soluble, well-folded trimers. Structural and antigenic analyses of two distinct HR1 redesigns confirm that redesigned Env closely mimics the native, prefusion trimer with a more stable gp41. Next, we replace the cleavage site between gp120 and gp41 with various linkers in the context of an HR1 redesign. Electron microscopy reveals a potential fusion intermediate state for uncleaved trimers containing short but not long linkers. Together, these results outline a general approach for stabilization of Env trimers from diverse HIV-1 strains.en
dc.language.isoen_USen
dc.publisherNature Publishing Groupen
dc.relation.isversionofdoi:10.1038/ncomms12040en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931249/pdf/en
dash.licenseLAAen_US
dc.titleUncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastabilityen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNature Communicationsen
dc.date.available2016-08-09T14:52:23Z
dc.identifier.doi10.1038/ncomms12040*
dash.authorsorderedfalse


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