9D32

Structure of the HKU5 RBD bound to the P. abramus ACE2 receptor

9D32 の概要

• エントリーDOI: 10.2210/pdb9d32/pdb
• EMDBエントリー: 46512
• 分子名称: Angiotensin-converting enzyme, Spike glycoprotein, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: mers-related hku5 coronaviruses, mersr-cov, spike glycoprotein, fusion protein, pipistrellus abramus ace2, structural genomics, seattle structural genomics center for infectious disease, ssgcid, inhibitor, viral protein-hydrolase complex, viral protein/hydrolase
• 由来する生物種: Pipistrellus abramus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 120600.17

構造登録者

Park, Y.J.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (登録日: 2024-08-09, 公開日: 2025-02-19, 最終更新日: 2025-04-02)

主引用文献

Park, Y.J.,Liu, C.,Lee, J.,Brown, J.T.,Ma, C.B.,Liu, P.,Gen, R.,Xiong, Q.,Zepeda, S.K.,Stewart, C.,Addetia, A.,Craig, C.J.,Tortorici, M.A.,Alshukairi, A.N.,Starr, T.N.,Yan, H.,Veesler, D.
Molecular basis of convergent evolution of ACE2 receptor utilization among HKU5 coronaviruses.
Cell, 188:1711-1728.e21, 2025

PubMed Abstract: DPP4 was considered a canonical receptor for merbecoviruses until the recent discovery of African bat-borne MERS-related coronaviruses using ACE2. The extent and diversity of ACE2 utilization among merbecoviruses and their receptor species tropism remain unknown. Here, we reveal that HKU5 enters host cells utilizing Pipistrellus abramus (P.abr) and several non-bat mammalian ACE2s through a binding mode distinct from that of any other known ACE2-using coronaviruses. We defined the molecular determinants of receptor species tropism and identified a single amino acid mutation enabling HKU5 to utilize human ACE2, providing proof of principle for machine-learning-assisted outbreak preparedness. We show that MERS-CoV and HKU5 have markedly distinct antigenicity and identified several HKU5 inhibitors, including two clinical compounds. Our findings profoundly alter our understanding of coronavirus evolution, as several merbecovirus clades independently evolved ACE2 utilization, and pave the way for developing countermeasures against viruses poised for human emergence.

PubMed: 39922192
DOI: 10.1016/j.cell.2024.12.032

実験手法

ELECTRON MICROSCOPY (3.1 Å)