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PMID: 16081124 Published · ppublish English Journal Article

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.

Virology ·Vol. 341 ·No. 1 ·2005-10-10 ·Pages 122-9

Follis KE, York J, Nunberg JH

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

MeSH Terms
Amino Acid Sequence Animals COS Cells Chlorocebus aethiops Membrane Fusion/genetics,physiology Membrane Glycoproteins/chemistry,genetics,physiology Models, Molecular Molecular Sequence Data Mutagenesis Protein Structure, Secondary Recombinant Proteins/chemistry,genetics Repetitive Sequences, Amino Acid SARS Virus/genetics,pathogenicity,physiology Spike Glycoprotein, Coronavirus Transfection Viral Envelope Proteins/chemistry,genetics,physiology
Chemicals
Membrane Glycoproteins Recombinant Proteins Spike Glycoprotein, Coronavirus Viral Envelope Proteins spike glycoprotein, SARS-CoV
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Follis Kathryn E
Montana Biotechnology Center, The University of Montana, Science Complex Room 221, Missoula, MT 59812, USA.
York Joanne
Nunberg Jack H
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Article Info
Journal
Virology
Abbr.
Virology
ISSN
0042-6822
DOI
10.1016/j.virol.2005.07.005
Published
2005-10-10
Pages
122-9
Language
English
Region
United States
NLM ID
0110674
PMCID
PMC7111819
Subset
IM
External Links
PubMed source DOI: 10.1016/j.virol.2005.07.005 PMC Full Text View journal details
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