Min Jin / Zaky Hassan / Zhijie Li / Ying Liu / Aleksandra Marakhovskaia / Alan H M Wong / Adam Forman / Mark Nitz / Michel Gilbert / Hai Yu / Xi Chen / James M Rini /
PubMed Abstract
The human coronavirus HKU1 uses both sialoglycoconjugates and the protein transmembrane serine protease 2 (TMPRSS2) as receptors. Carbohydrate binding leads to the spike protein up conformation ...The human coronavirus HKU1 uses both sialoglycoconjugates and the protein transmembrane serine protease 2 (TMPRSS2) as receptors. Carbohydrate binding leads to the spike protein up conformation required for TMPRSS2 binding, an outcome suggesting a distinct mechanism for driving fusion of the viral and host cell membranes. Nevertheless, the conformational changes promoted by carbohydrate binding have not been fully elucidated and the basis for HKU1's carbohydrate binding specificity remains unknown. Reported here are high resolution cryo-EM structures of the HKU1 spike protein trimer in its apo form and in complex with the carbohydrate moiety of a candidate carbohydrate receptor, the 9-O-acetylated GD3 ganglioside. The structures show that the spike monomer can exist in four discrete conformational states and that progression through them would promote the up conformation upon carbohydrate binding. We also show that a six-amino-acid insert is a determinant of HKU1's specificity for gangliosides containing a 9-O-acetylated α2-8-linked disialic acid moiety and that HKU1 shows weak affinity for the 9-O-acetylated sialic acids found on decoy receptors such as mucins.
EMDB-44875, PDB-9bsx: Cryo-EM structure of HCoV-HKU1 glycoprotein in complex with 9O-acetyl GD3 sialoglycan (DAA state) Method: EM (single particle) / Resolution: 2.37 Å
EMDB-44876, PDB-9bsy: Cryo-EM structure of HCoV-HKU1 glycoprotein in complex with 9O-acetyl GD3 sialoglycan (DAU state) Method: EM (single particle) / Resolution: 2.58 Å
EMDB-44877, PDB-9bsz: Cryo-EM structure of HCoV-HKU1 glycoprotein in complex with 9O-acetyl GD3 sialoglycan (AUU state) Method: EM (single particle) / Resolution: 2.49 Å
EMDB-44879, PDB-9bt1: Cryo-EM structure of HCoV-HKU1 glycoprotein in complex with 9O-acetyl GD3 sialoglycan (UUU state) Method: EM (single particle) / Resolution: 2.22 Å
EMDB-44885, PDB-9bta: Cryo-EM density map of HKU1 spike glycoprotein D1 domain in complex with 9O-acetyl GD3 sialoglycan (Down_alt state, locally refined) Method: EM (single particle) / Resolution: 2.39 Å
EMDB-44886, PDB-9btb: Cryo-EM density map of HKU1 spike glycoprotein D1 domain in complex with 9O-acetyl GD3 sialoglycan (Active state, locally refined) Method: EM (single particle) / Resolution: 2.33 Å
EMDB-44887, PDB-9btc: Cryo-EM density map of HKU1 spike glycoprotein D1 domain in complex with 9O-acetyl GD3 sialoglycan (Up state, locally refined) Method: EM (single particle) / Resolution: 2.41 Å
EMDB-44888, PDB-9btd: Cryo-EM structure of HCoV-HKU1 glycoprotein in complex with 9O-acetyl GD3 sialoglycan (DDA state) Method: EM (single particle) / Resolution: 2.43 Å
EMDB-48805, PDB-9n14: Cryo-EM structure of HCoV-HKU1 glycoprotein in complex with 9OAc-GD3(mutant T31VPR34 to GGGG) Method: EM (single particle) / Resolution: 3.08 Å
EMDB-48806, PDB-9n15: Cryo-EM structure of HCoV-HKU1 glycoprotein D1 Domain in complex with 9OAc-GD3(mutant T31VPR34 to GGGG) Method: EM (single particle) / Resolution: 3.2 Å
EMDB-48809, PDB-9n18: Cryo-EM structure of HCoV-HKU1 spike glycoprotein in complex with 9OAc-GD3 tetrasacchride (Deletion 33Pro34Arg) Method: EM (single particle) / Resolution: 3.02 Å
EMDB-48810, PDB-9n19: Cryo-EM structure of HCoV-HKU1spike glycoprotein D1 Domain in complex with 9OAc-GD3 tetrasacchride (Deletion 33Pro34Arg) Method: EM (single particle) / Resolution: 3.02 Å
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Keywords
human coronavirus hku1