Document Detail


Identification of residues in the receptor-binding domain (RBD) of the spike protein of human coronavirus NL63 that are critical for the RBD-ACE2 receptor interaction.
MedLine Citation:
PMID:  18343844     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human coronavirus NL63 (NL63), a member of the group I coronaviruses, may cause acute respiratory diseases in young children and immunocompromised adults. Like severe acute respiratory syndrome coronavirus (SARS-CoV), NL63 also employs the human angiotensin-converting enzyme 2 (hACE2) receptor for cellular entry. To identify residues in the spike protein of NL63 that are important for hACE2 binding, this study first generated a series of S1-truncated variants, examined their associations with the hACE2 receptor and subsequently mapped a minimal receptor-binding domain (RBD) that consisted of 141 residues (aa 476-616) towards the C terminus of the S1 domain. The data also demonstrated that the NL63 RBD bound to hACE2 more efficiently than its full-length counterpart and had a binding efficiency comparable to the S1 or RBD of SARS-CoV. A further series of RBD variants was generated using site-directed mutagenesis and random mutant library screening assays, and identified 15 residues (C497, Y498, V499, C500, K501, R518, R530, V531, G534, G537, D538, S540, E582, W585 and T591) that appeared to be critical for the RBD-hACE2 association. These critical residues clustered in three separate regions (designated RI, RII and RIII) inside the RBD, which may represent three receptor-binding sites. These results may help to delineate the molecular interactions between the S protein of NL63 and the hACE2 receptor, and may also enhance our understanding of the pathogenesis of NL63 and SARS-CoV.
Authors:
Han-Xin Lin; Yan Feng; Gillian Wong; Liping Wang; Bei Li; Xuesen Zhao; Yan Li; Fiona Smaill; Chengsheng Zhang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of general virology     Volume:  89     ISSN:  0022-1317     ISO Abbreviation:  J. Gen. Virol.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-17     Completed Date:  2008-06-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077340     Medline TA:  J Gen Virol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1015-24     Citation Subset:  IM    
Affiliation:
Department of Pathology and Molecular Medicine, McMaster University, Department of Microbiology, St Joseph's Healthcare, Hamilton, ON L8N 4A6, Canada.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Humans
Membrane Glycoproteins / chemistry*,  metabolism
Peptidyl-Dipeptidase A / metabolism*
Protein Binding
Protein Interaction Domains and Motifs / physiology
Protein Interaction Mapping
Receptors, Virus / metabolism*
SARS Virus / chemistry*,  metabolism
Severe Acute Respiratory Syndrome / virology
Viral Envelope Proteins / chemistry*,  metabolism
Chemical
Reg. No./Substance:
0/Membrane Glycoproteins; 0/Receptors, Virus; 0/Viral Envelope Proteins; 107476-75-5/spike glycoprotein, coronavirus; EC 3.4.15.1/Peptidyl-Dipeptidase A; EC 3.4.17.-/angiotensin converting enzyme 2

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