Cryo-EM structure of eastern equine encephalitis virus in complex with heparan sulfate analogues.

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TitleCryo-EM structure of eastern equine encephalitis virus in complex with heparan sulfate analogues.
Publication TypeJournal Article
Year of Publication2020
AuthorsChen, C-L, S Hasan, S, Klose, T, Sun, Y, Buda, G, Sun, C, Klimstra, WB, Rossmann, MG
JournalProc Natl Acad Sci U S A
Volume117
Issue16
Pagination8890-8899
Date Published2020 Apr 21
ISSN1091-6490
Abstract

Eastern equine encephalitis virus (EEEV), a mosquito-borne icosahedral alphavirus found mainly in North America, causes human and equine neurotropic infections. EEEV neurovirulence is influenced by the interaction of the viral envelope protein E2 with heparan sulfate (HS) proteoglycans from the host's plasma membrane during virus entry. Here, we present a 5.8-Å cryoelectron microscopy (cryo-EM) structure of EEEV complexed with the HS analog heparin. "Peripheral" HS binding sites were found to be associated with the base of each of the E2 glycoproteins that form the 60 quasi-threefold spikes (q3) and the 20 sites associated with the icosahedral threefold axes (i3). In addition, there is one HS site at the vertex of each q3 and i3 spike (the "axial" sites). Both the axial and peripheral sites are surrounded by basic residues, suggesting an electrostatic mechanism for HS binding. These residues are highly conserved among EEEV strains, and therefore a change in these residues might be linked to EEEV neurovirulence.

DOI10.1073/pnas.1910670117
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID32245806
PubMed Central IDPMC7183182
Grant ListR01 AI095436 / AI / NIAID NIH HHS / United States