9JMH

Cryo-EM structure of HKU25-BatCoV S-trimer stabilized with 2P and x1 disulfide bond

Summary for 9JMH

• Entry DOI: 10.2210/pdb9jmh/pdb
• EMDB information: 61602
• Descriptor: Spike glycoprotein,Fibritin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 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: Hypsugo bat coronavirus HKU25; More
• Total number of polymer chains: 3
• Total formula weight: 472924.34

Authors

Yuan, H.,Xiong, X. (deposition date: 2024-09-20, release date: 2025-06-18, Last modification date: 2025-07-23)

Primary citation

Yuan, H.,Wang, J.,Ma, Y.,Li, Z.,Gao, X.,Habib, G.,Liu, B.,Chen, J.,He, J.,Zhou, P.,Shi, Z.L.,Chen, X.,Xiong, X.
Structures and receptor binding activities of merbecovirus spike proteins reveal key signatures for human DPP4 adaptation.
Sci Adv, 11:eadv7296-eadv7296, 2025

PubMed Abstract: Merbecoviruses from bats, pangolins, and hedgehogs pose significant zoonotic threats, with a limited understanding of receptor binding by their spike (S) proteins. Here, we report cryo-EM structures of GD-BatCoV (BtCoV-422) and SE-PangolinCoV (MjHKU4r-CoV-1) RBDs in complex with human DPP4 (hDPP4). These structures exhibit a substantial offset in their hDPP4 interaction interfaces, revealing a conserved hydrophobic cluster as a convergent signature of DPP4 binding within the MERS-HKU4 clade of merbecoviruses. Structure-guided mutagenesis demonstrates that favorable interactions are distributed across multiple receptor binding motif (RBM) regions, working synergistically to confer high-affinity hDPP4 binding. Swapping of the merbecovirus RBM regions indicate limited plasticity and interchangeability among these regions. In addition, we report cryo-EM structures of six merbecovirus S-trimers. Structure-based phylogenetics suggests that hDPP4-binding merbecoviruses undergo convergent evolution, while ACE2-binding merbecoviruses exhibit diversification in their binding mechanisms. These findings offer critical insights into merbecovirus receptor utilization, providing a structural understanding for future surveillance.

PubMed: 40644548
DOI: 10.1126/sciadv.adv7296

Experimental method

ELECTRON MICROSCOPY (3 Å)