EMD-39043
Structure of HCoV-HKU1C spike in the inactive-2up conformation
EMD-39043
Single-particle3.62 Å
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Map released: 17/07/2024
Last modified: 23/10/2024
Sample Organism:
Human coronavirus HKU1,
Human coronavirus HKU1 (isolate N5)
Sample: HKU1C spike
Fitted models: 8y8e (Avg. Q-score: 0.207)
Deposition Authors: Lu YC, Zhang X, Wang HF, Sun L, Yang HT
Sample: HKU1C spike
Fitted models: 8y8e (Avg. Q-score: 0.207)
Deposition Authors: Lu YC, Zhang X, Wang HF, Sun L, Yang HT
TMPRSS2 and glycan receptors synergistically facilitate coronavirus entry.
Wang H,
Liu X,
Zhang X,
Zhao Z,
Lu Y,
Pu D,
Zhang Z,
Chen J,
Wang Y,
Li M,
Dong X,
Duan Y,
He Y,
Mao Q,
Guo H,
Sun H,
Zhou Y,
Yang Q,
Gao Y,
Yang X,
Cao H
,
Guddat L,
Sun L,
Rao Z,
Yang H
(2024) Cell , 187 , 4261
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(2024) Cell , 187 , 4261
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.
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.