EMD-39043

Single-particle
3.62 Å
EMD-39043 Deposition: 06/02/2024
Map released: 17/07/2024
Last modified: 23/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-39043

Structure of HCoV-HKU1C spike in the inactive-2up conformation

EMD-39043

Single-particle
3.62 Å
EMD-39043 Deposition: 06/02/2024
Map released: 17/07/2024
Last modified: 23/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
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
TMPRSS2 and glycan receptors synergistically facilitate coronavirus entry.
PUBMED: 38964329
DOI: doi:10.1016/j.cell.2024.06.016
ISSN: 1097-4172
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.