📄 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

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. © 2005 Elsevier Inc.

keywords 🔗 cell-cell fusion (34) 🔗 six-helix bundle (19) 🔗 acid sequence (108) 🔗 amino acid (454) 🔗 acid sequences (44) 🔗 important role (140) 🔗 fusion proteins (43) 🔗 viral fusion (38) 🔗 membrane fusion (105)

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