8ZUF

Cryo-EM structure of P.nat ACE2 mutant in complex with MOW15-22 RBD

Summary for 8ZUF

• Entry DOI: 10.2210/pdb8zuf/pdb
• EMDB information: 60483
• Descriptor: Angiotensin-converting enzyme, MOW15-22 RBD, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: ace2, rbd, viral protein/hydrolase, viral protein-hydrolase complex
• Biological source: Pipistrellus nathusii; More
• Total number of polymer chains: 2
• Total formula weight: 118235.04

Authors

Tang, J.,Deng, Z. (deposition date: 2024-06-09, release date: 2025-02-12, Last modification date: 2025-07-16)

Primary citation

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-, 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

Experimental method

ELECTRON MICROSCOPY (3.31 Å)