4.4 Å cryo-EM structure of an enveloped alphavirus Venezuelan equine encephalitis virus

Rui Zhang, Corey F. Hryc, Yao Cong, Xiangan Liu, Joanita Jakana, Rodion Gorchakov, Matthew L. Baker, Scott C. Weaver, Wah Chiu

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

Venezuelan equine encephalitis virus (VEEV), a member of the membrane-containing Alphavirus genus, is a human and equine pathogen, and has been developed as a biological weapon. Using electron cryo-microscopy (cryo-EM), we determined the structure of an attenuated vaccine strain, TC-83, of VEEV to 4.4 Å resolution. Our density map clearly resolves regions (including E1, E2 transmembrane helices and cytoplasmic tails) that were missing in the crystal structures of domains of alphavirus subunits. These new features are implicated in the fusion, assembly and budding processes of alphaviruses. Furthermore, our map reveals the unexpected E3 protein, which is cleaved and generally thought to be absent in the mature VEEV. Our structural results suggest a mechanism for the initial stage of nucleocapsid core formation, and shed light on the virulence attenuation, host recognition and neutralizing activities of VEEV and other alphavirus pathogens.

Original languageEnglish (US)
Pages (from-to)3854-3863
Number of pages10
JournalEMBO Journal
Volume30
Issue number18
DOIs
StatePublished - Sep 2011

Keywords

  • VEEV
  • alphavirus
  • bioweapon
  • cryo-EM
  • modelling

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Zhang, R., Hryc, C. F., Cong, Y., Liu, X., Jakana, J., Gorchakov, R., Baker, M. L., Weaver, S. C., & Chiu, W. (2011). 4.4 Å cryo-EM structure of an enveloped alphavirus Venezuelan equine encephalitis virus. EMBO Journal, 30(18), 3854-3863. https://doi.org/10.1038/emboj.2011.261