Acid-induced movements in the glycoprotein shell of an alphavirus turn the spikes into membrane fusion mode

Lars Haag, Henrik Garoff, Li Xing, Lena Hammar, Sin Tau Kan, R. Holland Cheng

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


In the icosahedral (T = 4) Semliki Forest virus, the envelope protomers, i.e. E1-E2 heterodimers, make one-to-one interactions with capsid proteins below the viral lipid bilayer, transverse the membrane and form an external glycoprotein shell with projections. The shell is organized by protomer domains interacting as hexamers and pentamers around shell openings at icosahedral 2- and 5-fold axes, respectively, and the projections by other domains associating as trimers at 3- and quasi 3-fold axes. We show here, using cryoelectron microscopy, that low pH, as occurs in the endosomes during virus uptake, results in the relaxation of protomer interactions around the 2- and the 5-fold axes in the shell, and movement of protomers towards 3- and quasi 3-fold axes in a way that reciprocally relocates their putative E1 and E2 domains. This seemed to be facilitated by a trimerization of transmembrane segments at the same axes. The alterations observed help to explain several key features of the spike-mediated membrane fusion reaction, including shell dissolution, heterodimer dissociation, fusion peptide exposure and E1 homotrimerization.

Original languageEnglish (US)
Pages (from-to)4402-4410
Number of pages9
JournalEMBO Journal
Issue number17
StatePublished - Sep 2 2002
Externally publishedYes


  • Alphavirus
  • Cryo-EM
  • Glycoprotein
  • Image reconstruction
  • Membrane fusion

ASJC Scopus subject areas

  • Genetics
  • Cell Biology


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