HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lin, H.-X. Articles by Zhang, C. Search for Related Content PubMed PubMed Citation Articles by Lin, H.-X. Articles by Zhang, C. Agricola Articles by Lin, H.-X. Articles by Zhang, C.

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

¹ Department of Pathology and Molecular Medicine, McMaster University and Department of Microbiology, St Joseph's Healthcare, Hamilton, ON L8N 4A6, Canada
² Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA
³ National Microbiology Laboratory, Canadian Science Center for Human and Animal Health, Winnipeg, MB R3E 3R2, Canada

Correspondence
Chengsheng Zhang
zhangch{at}mcmaster.ca

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.

This article has been cited by other articles:

				A. C. Mathewson, A. Bishop, Y. Yao, F. Kemp, J. Ren, H. Chen, X. Xu, B. Berkhout, L. van der Hoek, and I. M. Jones Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2 J. Gen. Virol., November 1, 2008; 89(11): 2741 - 2745. [Abstract] [Full Text] [PDF]