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

Kailang Wu, Weikai Li, Guiqing Peng, Fang Li

Research output: Contribution to journalArticlepeer-review

191 Scopus citations

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.

Original languageEnglish
Pages (from-to)19970-19974
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number47
DOIs
StatePublished - Nov 24 2009

Keywords

  • Receptor protein
  • SARS coronavirus
  • Spike protein receptor-binding domain
  • Virus-binding hotspots

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