6MWC

CryoEM structure of chimeric Eastern Equine Encephalitis Virus with Fab of EEEV-5 antibody

Summary for 6MWC

• Entry DOI: 10.2210/pdb6mwc/pdb
• EMDB information: 9249 9274 9275 9278 9279 9280 9281
• Descriptor: E1, E2, EEEV-5 antibody heavy chain, ... (4 entities in total)
• Functional Keywords: alphavirus, eeev, eastern equine encephalitis virus, sindbis, fab, virus-immune system complex, virus/immune system
• Biological source: Eastern equine encephalitis virus (EEEV); More
• Total number of polymer chains: 16
• Total formula weight: 567626.10

Authors

Hasan, S.S.,Sun, C.,Kim, A.S.,Watanabe, Y.,Chen, C.L.,Klose, T.,Buda, G.,Crispin, M.,Diamond, M.S.,Klimstra, W.B.,Rossmann, M.G. (deposition date: 2018-10-29, release date: 2018-12-19, Last modification date: 2019-12-18)

Primary citation

Hasan, S.S.,Sun, C.,Kim, A.S.,Watanabe, Y.,Chen, C.L.,Klose, T.,Buda, G.,Crispin, M.,Diamond, M.S.,Klimstra, W.B.,Rossmann, M.G.
Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization.
Cell Rep, 25:3136-3147.e5, 2018

PubMed Abstract: Alphaviruses are enveloped pathogens that cause arthritis and encephalitis. Here, we report a 4.4-Å cryoelectron microscopy (cryo-EM) structure of eastern equine encephalitis virus (EEEV), an alphavirus that causes fatal encephalitis in humans. Our analysis provides insights into viral entry into host cells. The envelope protein E2 showed a binding site for the cellular attachment factor heparan sulfate. The presence of a cryptic E2 glycan suggests how EEEV escapes surveillance by lectin-expressing myeloid lineage cells, which are sentinels of the immune system. A mechanism for nucleocapsid core release and disassembly upon viral entry was inferred based on pH changes and capsid dissociation from envelope proteins. The EEEV capsid structure showed a viral RNA genome binding site adjacent to a ribosome binding site for viral genome translation following genome release. Using five Fab-EEEV complexes derived from neutralizing antibodies, our investigation provides insights into EEEV host cell interactions and protective epitopes relevant to vaccine design.

PubMed: 30540945
DOI: 10.1016/j.celrep.2018.11.067

Experimental method

ELECTRON MICROSCOPY (7.5 Å)