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-Structure paper
| タイトル | Multiple independent acquisitions of ACE2 usage in MERS-related coronaviruses. |
|---|---|
| ジャーナル・号・ページ | Cell, Vol. 188, Issue 6, Page 1693-1710.e18, Year 2025 |
| 掲載日 | 2025年3月20日 |
著者 | Cheng-Bao Ma / Chen Liu / Young-Jun Park / Jingjing Tang / Jing Chen / Qing Xiong / Jimin Lee / Cameron Stewart / Daniel Asarnow / Jack Brown / M Alejandra Tortorici / Xiao Yang / Ye-Hui Sun / Yuan-Mei Chen / Xiao Yu / Jun-Yu Si / Peng Liu / Fei Tong / Mei-Ling Huang / Jing Li / Zheng-Li Shi / Zengqin Deng / David Veesler / Huan Yan / ![]() |
| PubMed 要旨 | The angiotensin-converting enzyme 2 (ACE2) receptor is shared by various coronaviruses with distinct receptor-binding domain (RBD) architectures, yet our understanding of these convergent acquisition ...The angiotensin-converting enzyme 2 (ACE2) receptor is shared by various coronaviruses with distinct receptor-binding domain (RBD) architectures, yet our understanding of these convergent acquisition events remains elusive. Here, we report that two bat MERS-related coronaviruses (MERSr-CoVs) infecting Pipistrellus nathusii (P.nat)-MOW15-22 and PnNL2018B-use ACE2 as their receptor, with narrow ortholog specificity. Cryoelectron microscopy structures of the MOW15-22/PnNL2018B RBD-ACE2 complexes unveil an unexpected and entirely distinct binding mode, mapping >45 Å away from that of any other known ACE2-using coronaviruses. Functional profiling of ACE2 orthologs from 105 mammalian species led to the identification of host tropism determinants, including an ACE2 N432-glycosylation restricting viral recognition, and the design of a soluble P.nat ACE2 mutant with potent viral neutralizing activity. Our findings reveal convergent acquisition of ACE2 usage for merbecoviruses found in European bats, underscoring the extraordinary diversity of ACE2 recognition modes among coronaviruses and the promiscuity of this receptor. |
リンク | Cell / PubMed:39922191 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.4 - 3.31 Å |
| 構造データ | EMDB-45253, PDB-9c6o: EMDB-46691, PDB-9dak: EMDB-60483, PDB-8zuf: |
| 化合物 | ![]() ChemComp-NAG: ![]() ChemComp-ZN: ![]() ChemComp-HOH: |
| 由来 |
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キーワード | VIRAL PROTEIN/HYDROLASE / ACE2 / RBD / VIRAL PROTEIN-HYDROLASE complex / VIRAL PROTEIN / Merbecovirus / MERS-related coronaviruses / MOW15-22 Spike glycoprotein / fusion protein / P. davyi ACE2 / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / Spike glycoprotein / inhibitor |
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Sarbecovirus (ウイルス)
pteronotus davyi (ケナシコウモリ)
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