7N69

Pre-fusion state 2 of EEEV with localized reconstruction

Summary for 7N69

• Entry DOI: 10.2210/pdb7n69/pdb
• EMDB information: 24201
• Descriptor: Spike glycoprotein E1, Spike glycoprotein E2 (2 entities in total)
• Functional Keywords: eeev, pre-fusion, localized reconstruction, virus
• Biological source: Eastern equine encephalitis virus (strain Florida 91-469) (EEEV, Eastern equine encephalomyelitis virus); More
• Total number of polymer chains: 12
• Total formula weight: 569910.56

Authors

Chen, C.-L.,Kuhn, R.J.,Klose, T. (deposition date: 2021-06-07, release date: 2022-06-22, Last modification date: 2024-10-16)

Primary citation

Chen, C.L.,Klose, T.,Sun, C.,Kim, A.S.,Buda, G.,Rossmann, M.G.,Diamond, M.S.,Klimstra, W.B.,Kuhn, R.J.
Cryo-EM structures of alphavirus conformational intermediates in low pH-triggered prefusion states.
Proc.Natl.Acad.Sci.USA, 119:e2114119119-e2114119119, 2022

PubMed Abstract: 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.

PubMed: 35867819
DOI: 10.1073/pnas.2114119119

Experimental method

ELECTRON MICROSCOPY (14.1 Å)