Importance of SARS-CoV spike protein Trp-rich region in viral infectivity |
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Authors: | Lu Yanning Neo Tuan Ling Liu Ding Xiang Tam James P |
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Affiliation: | a School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore b Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore c The Scripps Research Institute, 5353 Parkside Drive, Jupiter, FL 33458, USA d Beijing Center for Diseases Prevention and Control, 16 Hepingli Middle Street, Dongcheng District, Beijing 100013, China |
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Abstract: | SARS-CoV entry is mediated by spike glycoprotein. During the viral and host cellular membrane fusion, HR1 and HR2 form 6-helix bundle, positioning the fusion peptide closely to the C-terminal region of ectodomain to drive apposition and subsequent membrane fusion. Connecting to the HR2 region is a Trp-rich region which is absolutely conserved in members of coronaviruses. To investigate the importance of Trp-rich region in SARS-CoV entry, we produced different mutated S proteins using Alanine scan strategy. SARS-CoV pseudotyped with mutated S protein was used to measure viral infectivity. To restore the aromaticity of Ala-mutants, we performed rescue experiments using phenylalanine substitutions. Our results show that individually substituted Ala-mutants substantially decrease infectivity by >90%, global Ala-mutants totally abrogated infectivity. In contrast, Phe-substituted mutants are able to restore 10-25% infectivity comparing to the wild-type. The results suggest that the Trp-rich region of S protein is essential for SARS-CoV infectivity. |
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Keywords: | Trp-rich region SARS-CoV Spike protein Membrane fusion Alanine scan Mutant Infectivity |
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