8ZY1

Sarbecovirus BM48-31 Spike Trimer in a Locked Conformation

Summary for 8ZY1

• Entry DOI: 10.2210/pdb8zy1/pdb
• EMDB information: 60552
• Descriptor: Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: spike protein, viral protein
• Biological source: Bat coronavirus BM48-31/BGR/2008
• Total number of polymer chains: 3
• Total formula weight: 436332.12

Authors

Wang, J.,Xiong, X. (deposition date: 2024-06-16, release date: 2025-02-05, Last modification date: 2025-06-18)

Primary citation

Wang, J.,Ma, Y.,Li, Z.,Yuan, H.,Liu, B.,Li, Z.,Su, M.,Habib, G.,Liu, Y.,Fu, L.,Wang, P.,Li, M.,He, J.,Chen, J.,Zhou, P.,Shi, Z.,Chen, X.,Xiong, X.
SARS-related coronavirus S-protein structures reveal synergistic RBM interactions underpinning high-affinity human ACE2 binding.
Sci Adv, 11:eadr8772-eadr8772, 2025

PubMed Abstract: High-affinity and specific binding toward the human angiotensin-converting enzyme 2 (hACE2) receptor by severe acute respiratory syndrome coronavirus (SARS)-related coronaviruses (SARSr-CoVs) remains incompletely understood. We report cryo-electron microscopy structures of eight different S-proteins from SARSr-CoVs found across Asia, Europe, and Africa. These S-proteins all adopt tightly packed, locked, prefusion conformations. These structures enable the classification of SARSr-CoV S-proteins into three types, based on their receptor-binding motif (RBM) structures and ACE2 binding characteristics. Type-2 S-proteins often preferentially bind bat ACE2 (bACE2) over hACE2. We report a structure of a type-2 BtKY72-RBD in complex with bACE2 to understand ACE2 specificity. Structure-guided mutagenesis of BtKY72-RBD reveals that multiple synergistic mutations in four different regions of RBM are required to achieve high-affinity hACE2 binding. Similar RBM changes can also confer hACE2 binding to another type-2 BM48-31 S-protein, which is primarily non-ACE2 binding. These results provide an understanding of how high-affinity hACE2 binding may be acquired by SARSr-CoV S-proteins.

PubMed: 40085715
DOI: 10.1126/sciadv.adr8772

Experimental method

ELECTRON MICROSCOPY (3.1 Å)