Serine-scanning mutagenesis studies of the C-terminal heptad repeats in the SARS coronavirus S glycoprotein highlight the important role of the short helical region

Kathryn E. Follis, Joanne York, Jack H. Nunberg

Research output: Contribution to journalArticlepeer-review

Abstract

The fusion subunit of the SARS-CoV S glycoprotein contains two regions of hydrophobic heptad-repeat amino acid sequences that have been shown in biophysical studies to form a six-helix bundle structure typical of the fusion-active core found in Class I viral fusion proteins. Here, we have applied serine-scanning mutagenesis to the C-terminal-most heptad-repeat region in the SARS-CoV S glycoprotein to investigate the functional role of this region in membrane fusion. We show that hydrophobic sidechains at a and d positions only within the short helical segment of the C-terminal heptad-repeat region (I1161, I1165, L1168, A1172, and L1175) are critical for cell-cell fusion. Serine mutations at outlying heptad-repeat residues that form an extended chain in the core structure (V1158, L1179, and L1182) do not affect fusogenicity. Our study provides genetic evidence for the important role of α-helical packing in promoting S glycoprotein-mediated membrane fusion.

Original languageEnglish
Pages (from-to)122-129
Number of pages8
JournalVirology
Volume341
Issue number1
DOIs
StatePublished - Oct 10 2005

Keywords

  • Coronavirus
  • Envelope glycoprotein
  • Membrane fusion
  • Mutagenesis
  • SARS
  • Six-helix bundle
  • Spike glycoprotein

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