Characterization of an early-stage fusion intermediate of Sindbis virus using cryoelectron microscopy

Sheng Cao, Wei Zhang

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28 Scopus citations


The sequential steps in the alphavirus membrane fusion pathway have been postulated based on the prefusion and postfusion crystal structures of the viral fusion protein E1 in conjunction with biochemical studies. However, the molecular structures of the hypothesized fusion intermediates have remained obscure due to difficulties inherent in the dynamic nature of the process. We developed an experimental system that uses liposomes as the target membrane to capture Sindbis virus, a prototypical alphavirus, in its membrane-binding form at pH 6.4. Cryoelectron micrograph analyses and 3D reconstructions showed that the virus retains its overall icosahedral structure at this mildly acidic pH, except in the membrane-binding region, where monomeric E1 associates with the target membrane and the E2 glycoprotein retains its original trimeric organization. The remaining E2 trimers may hinder E1 homotrimerization and are a potential target for antiviral drugs.

Original languageEnglish (US)
Pages (from-to)13362-13367
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number33
StatePublished - Aug 13 2013


  • Class II viral fusion protein
  • Enveloped viruses
  • Image processing
  • Protein organization
  • Viral entry


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