TMPRSS2 and glycan receptors synergistically facilitate coronavirus entry.
Cell
; 187(16): 4261-4271.e17, 2024 Aug 08.
Article
en En
| MEDLINE
| ID: mdl-38964329
ABSTRACT
The entry of coronaviruses is initiated by spike recognition of host cellular receptors, involving proteinaceous and/or glycan receptors. Recently, TMPRSS2 was identified as the proteinaceous receptor for HCoV-HKU1 alongside sialoglycan as a glycan receptor. However, the underlying mechanisms for viral entry remain unknown. Here, we investigated the HCoV-HKU1C spike in the inactive, glycan-activated, and functionally anchored states, revealing that sialoglycan binding induces a conformational change of the NTD and promotes the neighboring RBD of the spike to open for TMPRSS2 recognition, exhibiting a synergistic mechanism for the entry of HCoV-HKU1. The RBD of HCoV-HKU1 features an insertion subdomain that recognizes TMPRSS2 through three previously undiscovered interfaces. Furthermore, structural investigation of HCoV-HKU1A in combination with mutagenesis and binding assays confirms a conserved receptor recognition pattern adopted by HCoV-HKU1. These studies advance our understanding of the complex viral-host interactions during entry, laying the groundwork for developing new therapeutics against coronavirus-associated diseases.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Serina Endopeptidasas
/
Internalización del Virus
/
Glicoproteína de la Espiga del Coronavirus
Idioma:
En
Revista:
Cell
Año:
2024
Tipo del documento:
Article