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-Structure paper
タイトル | Cryo-EM structures of alphavirus conformational intermediates in low pH-triggered prefusion states. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 119, Issue 30, Page e2114119119, Year 2022 |
掲載日 | 2022年7月26日 |
著者 | Chun-Liang Chen / Thomas Klose / Chengqun Sun / Arthur S Kim / Geeta Buda / Michael G Rossmann / Michael S Diamond / William B Klimstra / Richard J Kuhn / |
PubMed 要旨 | Alphaviruses can cause severe human arthritis and encephalitis. During virus infection, structural changes of viral glycoproteins in the acidified endosome trigger virus-host membrane fusion for ...Alphaviruses can cause severe human arthritis and encephalitis. During virus infection, structural changes of viral glycoproteins in the acidified endosome trigger virus-host membrane fusion for delivery of the capsid core and RNA genome into the cytosol to initiate virus translation and replication. However, mechanisms by which E1 and E2 glycoproteins rearrange in this process remain unknown. Here, we investigate prefusion cryoelectron microscopy (cryo-EM) structures of eastern equine encephalitis virus (EEEV) under acidic conditions. With models fitted into the low-pH cryo-EM maps, we suggest that E2 dissociates from E1, accompanied by a rotation (∼60°) of the E2-B domain (E2-B) to expose E1 fusion loops. Cryo-EM reconstructions of EEEV bound to a protective antibody at acidic and neutral pH suggest that stabilization of E2-B prevents dissociation of E2 from E1. These findings reveal conformational changes of the glycoprotein spikes in the acidified host endosome. Stabilization of E2-B may provide a strategy for antiviral agent development. |
リンク | Proc Natl Acad Sci U S A / PubMed:35867819 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 5.1 - 18.2 Å |
構造データ | EMDB-24199: Localized reconstruction of EEEV EMDB-24200: Pre-fusion state 2 of EEEV EMDB-24201: Late pre-fusion state of EEEV (pH 5.5) with localized reconstruction EMDB-24202: EEEV in complex with Fab22 at acidic pH (pH 5.5) EMDB-24203: EEEV in complex with Fab22 at neutral pH (pH 7.4) EMDB-24204: Pre-fusion state 1 of EEEV EMDB-24205: Early pre-fusion state of EEEV (pH 5.5) with localized reconstruction |
由来 |
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キーワード | VIRUS / EEEV / pre-fusion / localized reconstruction |