8VGT

Structure of the HKU1 RBD bound to the human TMPRSS2 receptor

8VGT の概要

• エントリーDOI: 10.2210/pdb8vgt/pdb
• EMDBエントリー: 43224
• 分子名称: Spike protein S1, Transmembrane protease serine 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: spike glycoprotein, fusion protein, structural genomics, seattle structural genomics center for infectious disease, ssgcid, inhibitor, viral protein
• 由来する生物種: Human coronavirus HKU1 (isolate N1); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84641.81

構造登録者

Park, Y.J.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (登録日: 2023-12-27, 公開日: 2024-03-06, 最終更新日: 2024-10-16)

主引用文献

McCallum, M.,Park, Y.J.,Stewart, C.,Sprouse, K.R.,Addetia, A.,Brown, J.,Tortorici, M.A.,Gibson, C.,Wong, E.,Ieven, M.,Telenti, A.,Veesler, D.
Human coronavirus HKU1 recognition of the TMPRSS2 host receptor.
Cell, 187:4231-, 2024

PubMed Abstract: The human coronavirus HKU1 spike (S) glycoprotein engages host cell surface sialoglycans and transmembrane protease serine 2 (TMPRSS2) to initiate infection. The molecular basis of HKU1 binding to TMPRSS2 and determinants of host receptor tropism remain elusive. We designed an active human TMPRSS2 construct enabling high-yield recombinant production in human cells of this key therapeutic target. We determined a cryo-electron microscopy structure of the HKU1 RBD bound to human TMPRSS2, providing a blueprint of the interactions supporting viral entry and explaining the specificity for TMPRSS2 among orthologous proteases. We identified TMPRSS2 orthologs from five mammalian orders promoting HKU1 S-mediated entry into cells along with key residues governing host receptor usage. Our data show that the TMPRSS2 binding motif is a site of vulnerability to neutralizing antibodies and suggest that HKU1 uses S conformational masking and glycan shielding to balance immune evasion and receptor engagement.

PubMed: 38964328
DOI: 10.1016/j.cell.2024.06.006

実験手法

ELECTRON MICROSCOPY (2.9 Å)