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

Journal Article · Mon Oct 10 04:00:00 EDT 2005 · Virology

DOI:https://doi.org/10.1016/j.virol.2005.07.005· OSTI ID:20729137

Follis, Kathryn E ^[1]; York, Joanne ^[1]; Nunberg, Jack H ^[1]

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1. Montana Biotechnology Center, University of Montana, Science Complex Room 221, Missoula, MT 59812 (United States)

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 {alpha}-helical packing in promoting S glycoprotein-mediated membrane fusion.

• OSTI ID: 20729137
• Journal Information: Virology, Journal Name: Virology Journal Issue: 1 Vol. 341; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINO ACID SEQUENCE
GLYCOPROTEINS
MUTAGENESIS
MUTATIONS
SERINE