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TitleMolecular basis of host recognition of human coronavirus 229E.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 2045, Year 2025
Publish dateFeb 27, 2025
AuthorsYu-Xi Tsai / Yu-Chun Chien / Min-Feng Hsu / Kay-Hooi Khoo / Shang-Te Danny Hsu /
PubMed AbstractHuman coronavirus 229E (HCoV-229E) is the earliest CoV found to infect humans. It binds to the human aminopeptidase N (hAPN) through the receptor binding domain (RBD) of its spike (S) protein to ...Human coronavirus 229E (HCoV-229E) is the earliest CoV found to infect humans. It binds to the human aminopeptidase N (hAPN) through the receptor binding domain (RBD) of its spike (S) protein to achieve host recognition. We present the cryo-electron microscopy structure of two HCoV-229E S protein in complex with a dimeric hAPN to provide structural insights on how the HCoV-229E S protein opens up its RBD to engage with its host receptor, information that is currently missing among alphacoronaviruses to which HCoV-229E belong. We quantitatively profile the glycosylation of HCoV-229E S protein and hAPN to deduce the glyco-shielding effects pertinent to antigenicity and host recognition. Finally, we present an atomic model of fully glycosylated HCoV-229E S in complex with hAPN anchored on their respective membrane bilayers to recapitulate the structural basis of the first step of host infection by HCoV-229E.
External linksNat Commun / PubMed:40016196 / PubMed Central
MethodsEM (single particle)
Resolution3.23 - 4.37 Å
Structure data

EMDB-37462, PDB-8wde:
CryoEM structure of the spike protein of human CoV 229E in complex with receptor hAPN (composite map)
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-38816: Local refinement of receptor binding domain and hinge region of single S protein
Method: EM (single particle) / Resolution: 3.23 Å

EMDB-38817: Local refinement of monomeric hAPN
Method: EM (single particle) / Resolution: 3.73 Å

EMDB-38818: Local refinement of dimeric hAPN and the receptor binding domain as well as the hinge region of single S protein
Method: EM (single particle) / Resolution: 3.61 Å

EMDB-38819: Local refinement of monomeric hAPN and receptor binding domain of single S protein
Method: EM (single particle) / Resolution: 3.57 Å

EMDB-38820: Local refinement of single HCoV-229E S protein
Method: EM (single particle) / Resolution: 3.39 Å

EMDB-38821: Local refinement of monomeric hAPN and single HCoV-229E S protein
Method: EM (single particle) / Resolution: 3.71 Å

EMDB-38822: CryoEM structure of the spike protein of human CoV 229E in complex with receptor hAPN
Method: EM (single particle) / Resolution: 4.37 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • human coronavirus 229e
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / human aminopeptidase N

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