9DAK

Merbecovirus PnNL2018B Spike glycoprotein RBD bound to the P. Nathusii ACE2

9DAK の概要

• エントリーDOI: 10.2210/pdb9dak/pdb
• EMDBエントリー: 46691
• 分子名称: ACE2, Spike glycoprotein receptor binding domain, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: merbecovirus, spike glycoprotein, fusion protein, structural genomics, seattle structural genomics center for infectious disease, ssgcid, inhibitor, viral protein
• 由来する生物種: Pipistrellus nathusii; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 140997.48

構造登録者

Park, Y.J.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (登録日: 2024-08-22, 公開日: 2025-02-19, 最終更新日: 2025-04-02)

主引用文献

Ma, C.B.,Liu, C.,Park, Y.J.,Tang, J.,Chen, J.,Xiong, Q.,Lee, J.,Stewart, C.,Asarnow, D.,Brown, J.,Tortorici, M.A.,Yang, X.,Sun, Y.H.,Chen, Y.M.,Yu, X.,Si, J.Y.,Liu, P.,Tong, F.,Huang, M.L.,Li, J.,Shi, Z.L.,Deng, Z.,Veesler, D.,Yan, H.
Multiple independent acquisitions of ACE2 usage in MERS-related coronaviruses.
Cell, 188:1693-1710.e18, 2025

PubMed Abstract: 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.

PubMed: 39922191
DOI: 10.1016/j.cell.2024.12.031

実験手法

ELECTRON MICROSCOPY (2.4 Å)