A Stable Prefusion Intermediate of the Alphavirus Fusion Protein Reveals Critical Features of Class II Membrane Fusion

Claudia Sánchez-San Martín, Hernando Sosa, Margaret Kielian

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32 Scopus citations


Alphaviruses infect cells via a low-pH-triggered membrane fusion reaction mediated by the class II virus fusion protein E1, an elongated molecule with three extramembrane domains (DI-III). E1 drives fusion by inserting its fusion peptide loop into the target membrane and refolding to a hairpin-like trimer in which DIII moves toward the target membrane and packs against the central trimer. Three-dimensional structures provide static pictures of prefusion and postfusion E1 but do not explain this transition. Using truncated forms of E1, we reconstituted a low-pH-dependent intermediate composed of trimers of DI/II. Unexpectedly, DI/II trimers were stable in the absence of DIII. Once formed at a low pH, DI/II trimers efficiently and specifically bound recombinant DIII through a pH-independent reaction. Even in the absence of DIII, DI/II trimers interacted to form hexagonal lattices and to cause membrane deformation and tubulation. These studies identify a prefusion intermediate in class II membrane fusion.

Original languageEnglish (US)
Pages (from-to)600-608
Number of pages9
JournalCell Host and Microbe
Issue number6
Publication statusPublished - Dec 11 2008




ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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