6ODF

EEEV glycoproteins bound with heparan sulfate

Summary for 6ODF

• Entry DOI: 10.2210/pdb6odf/pdb
• EMDB information: 20019
• Descriptor: E1, E2, 2-O-sulfo-beta-L-galactopyranuronic acid-(1-4)-[(2R,3R,4R,5R,6R)-2,4,5-trihydroxy-6-(sulfooxy)tetrahydro-2H-pyran-3-yl]sulfamic acid (3 entities in total)
• Functional Keywords: eeev, virus
• Biological source: Eastern equine encephalitis virus (EEEV); More
• Total number of polymer chains: 8
• Total formula weight: 383429.13

Authors

Rossmann, M.G.,Chen, C.L. (deposition date: 2019-03-26, release date: 2020-04-01, Last modification date: 2024-11-20)

Primary citation

Chen, C.L.,Hasan, S.S.,Klose, T.,Sun, Y.,Buda, G.,Sun, C.,Klimstra, W.B.,Rossmann, M.G.
Cryo-EM structure of eastern equine encephalitis virus in complex with heparan sulfate analogues.
Proc.Natl.Acad.Sci.USA, 117:8890-8899, 2020

PubMed 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.

PubMed: 32245806
DOI: 10.1073/pnas.1910670117

Experimental method

ELECTRON MICROSCOPY (5.8 Å)