Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor
- PMID: 19901337
- PMCID: PMC2785276
- DOI: 10.1073/pnas.0908837106
Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor
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 beta-sandwich core structure consisting of 2 layers of beta-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.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
Similar articles
-
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.J Gen Virol. 2008 Apr;89(Pt 4):1015-1024. doi: 10.1099/vir.0.83331-0. J Gen Virol. 2008. PMID: 18343844
-
Structural analysis of major species barriers between humans and palm civets for severe acute respiratory syndrome coronavirus infections.J Virol. 2008 Jul;82(14):6984-91. doi: 10.1128/JVI.00442-08. Epub 2008 Apr 30. J Virol. 2008. PMID: 18448527 Free PMC article.
-
Highly conserved regions within the spike proteins of human coronaviruses 229E and NL63 determine recognition of their respective cellular receptors.J Virol. 2006 Sep;80(17):8639-52. doi: 10.1128/JVI.00560-06. J Virol. 2006. PMID: 16912312 Free PMC article.
-
Insights from the association of SARS-CoV S-protein with its receptor, ACE2.Adv Exp Med Biol. 2006;581:209-18. doi: 10.1007/978-0-387-33012-9_36. Adv Exp Med Biol. 2006. PMID: 17037532 Free PMC article. Review. No abstract available.
-
Attachment factor and receptor engagement of SARS coronavirus and human coronavirus NL63.Adv Exp Med Biol. 2006;581:219-27. doi: 10.1007/978-0-387-33012-9_37. Adv Exp Med Biol. 2006. PMID: 17037533 Free PMC article. Review. No abstract available.
Cited by
-
Molecular basis of convergent evolution of ACE2 receptor utilization among HKU5 coronaviruses.bioRxiv [Preprint]. 2024 Aug 28:2024.08.28.608351. doi: 10.1101/2024.08.28.608351. bioRxiv. 2024. PMID: 39253417 Free PMC article. Preprint.
-
Structural basis for mouse receptor recognition by bat SARS2-like coronaviruses.Proc Natl Acad Sci U S A. 2024 Aug 6;121(32):e2322600121. doi: 10.1073/pnas.2322600121. Epub 2024 Jul 31. Proc Natl Acad Sci U S A. 2024. PMID: 39083418 Free PMC article.
-
Molecular determinants of cross-species transmission in emerging viral infections.Microbiol Mol Biol Rev. 2024 Sep 26;88(3):e0000123. doi: 10.1128/mmbr.00001-23. Epub 2024 Jun 24. Microbiol Mol Biol Rev. 2024. PMID: 38912755 Review.
-
The Inhibitory Effects of the Herbals Secondary Metabolites (7α-acetoxyroyleanone, Curzerene, Incensole, Harmaline, and Cannabidiol) on COVID-19: A Molecular Docking Study.Recent Pat Biotechnol. 2024;18(4):316-331. doi: 10.2174/0118722083246773231108045238. Recent Pat Biotechnol. 2024. PMID: 38817009
-
Seasonal human coronavirus NL63 epidemics in children in Guilin, China, reveal the emergence of a new subgenotype of HCoV-NL63.Front Cell Infect Microbiol. 2024 Apr 26;14:1378804. doi: 10.3389/fcimb.2024.1378804. eCollection 2024. Front Cell Infect Microbiol. 2024. PMID: 38736749 Free PMC article.
References
-
- Baranowski E, Ruiz-Jarabo CM, Domingo E. Evolution of cell recognition by viruses. Science. 2001;292:1102–1105. - PubMed
-
- Bewley MC, Springer K, Zhang YB, Freimuth P, Flanagan JM. Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR. Science. 1999;286:1579–1583. - PubMed
-
- Carfi A, et al. Herpes simplex virus glycoprotein D bound to the human receptor HveA. Mol Cell. 2001;8:169–179. - PubMed
-
- Li F, Li WH, Farzan M, Harrison SC. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science. 2005;309:1864–1868. - PubMed
Publication types
MeSH terms
Substances
Associated data
- Actions
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous