8Y88
Structure of HCoV-HKU1C spike in the functionally anchored-2up conformation with 2TMPRSS2
Summary for 8Y88
Entry DOI | 10.2210/pdb8y88/pdb |
EMDB information | 39037 |
Descriptor | Spike glycoprotein, Transmembrane protease serine 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
Functional Keywords | hku1a, spike, tmprss2, viral protein |
Biological source | Human coronavirus HKU1 More |
Total number of polymer chains | 5 |
Total formula weight | 511136.11 |
Authors | Lu, Y.C.,Zhang, X.,Wang, H.F.,Liu, X.C.,Sun, L.,Yang, H.T. (deposition date: 2024-02-06, release date: 2024-07-17, Last modification date: 2024-11-27) |
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 (3.03 Å) |
Structure validation
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