Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor

doi:10.1073/pnas.0908837106

Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor

^aDepartment of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455; and
^bDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115

Edited by John Johnson, Scripps Research Institute, La Jolla, CA, and accepted by the Editorial Board September 21, 2009
↵¹K.W. and W.L. contributed equally to this work. (received for review August 4, 2009)

Abstract

NL63 coronavirus (NL63-CoV), a prevalent human respiratory virus, is the only group I coronavirus known to use angiotensin-converting enzyme 2 (ACE2) as its receptor. Incidentally, ACE2 is also used by group II SARS coronavirus (SARS-CoV). We investigated how different groups of coronaviruses recognize the same receptor, whereas homologous group I coronaviruses recognize different receptors. We determined the crystal structure of NL63-CoV spike protein receptor-binding domain (RBD) complexed with human ACE2. NL63-CoV RBD has a novel β-sandwich core structure consisting of 2 layers of β-sheets, presenting 3 discontinuous receptor-binding motifs (RBMs) to bind ACE2. NL63-CoV and SARS-CoV have no structural homology in RBD cores or RBMs; yet the 2 viruses recognize common ACE2 regions, largely because of a “virus-binding hotspot” on ACE2. Among group I coronaviruses, RBD cores are conserved but RBMs are variable, explaining how these viruses recognize different receptors. These results provide a structural basis for understanding viral evolution and virus–receptor interactions.

Footnotes

²To whom correspondence should be addressed. E-mail: lifang{at}umn.edu
Author contributions: F.L. designed reseach; K.W., W.L., and G.P. performed research; K.W., W.L., G.P., and F.L. analyzed data; and F.L. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. J.J. is a guest editor invited by the Editorial Board.
Data deposition: Coordinate and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 3KBH).
This article contains supporting information online at www.pnas.org/cgi/content/full/0908837106/DCSupplemental.