8Y8G
Structure of HCoV-HKU1C spike in the glycan-activated-1up conformation
This is a non-PDB format compatible entry.
Summary for 8Y8G
| Entry DOI | 10.2210/pdb8y8g/pdb |
| EMDB information | 39045 |
| Descriptor | Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
| Functional Keywords | hku1c, spike, tmprss2, viral protein |
| Biological source | Human coronavirus HKU1 (isolate N5) (HCoV-HKU1) |
| Total number of polymer chains | 3 |
| Total formula weight | 427435.67 |
| Authors | Lu, Y.C.,Zhang, X.,Wang, H.F.,Sun, L.,Yang, H.T. (deposition date: 2024-02-06, release date: 2024-07-17, Last modification date: 2024-11-06) |
| Primary citation | 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. TMPRSS2 and glycan receptors synergistically facilitate coronavirus entry. Cell, 187:4261-, 2024 Cited by PubMed 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. PubMed: 38964329DOI: 10.1016/j.cell.2024.06.016 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.23 Å) |
Structure validation
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