8XYM

Cryo-EM structure of CX1 spike protein (6P)

Summary for 8XYM

• Entry DOI: 10.2210/pdb8xym/pdb
• EMDB information: 38778
• Descriptor: Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: cx1, spike protein, viral protein
• Biological source: Coronavirinae
• Total number of polymer chains: 3
• Total formula weight: 428938.67

Authors

Xu, Z.P.,Li, L.J.,Gu, Y.H.,Qi, J.X.,Gao, G.F. (deposition date: 2024-01-20, release date: 2025-01-22, Last modification date: 2025-09-03)

Primary citation

Xu, Z.,Li, L.,Gu, Y.,Li, D.,Qi, J.,Liu, K.,Deng, C.X.,Gao, G.F.
CX1/BtSY2 and BANAL-20-52 exhibit broader receptor binding and higher affinities to multiple animal ACE2 orthologs than SARS-CoV-2 prototype.
J.Virol., 99:-, 2025

PubMed Abstract: Animal coronaviruses (CoVs) CX1 (formerly named BtSY2) and BANAL-20-52 are phylogenetically closely related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and CX1 is the first observed animal betaCoV carrying naturally occurring Y501 in its receptor-binding domain (RBD) of the spike (S) protein, a residue related to human adaptation and broader host range. We evaluated the ACE2 usage of CX1 and BANAL-20-52 and observed broader receptor binding spectra and higher affinities to most of the tested animal ACE2 orthologs than the SARS-CoV-2 prototype. Determination of the cryo-EM structures of their S proteins and RBD/hACE2 complexes reveals that Y501 is inter-replaceable with H498 substitution while synergetic with R498 for human ACE2 binding. These results provide further structural insights into SARS-CoV-2 receptor recognition and address the importance of surveillance on potential emerging CoVs.IMPORTANCESince the outbreak of COVID-19, forewarning and prevention of the next pandemic have been widely discussed. Coronaviruses (CoVs) CX1 (formerly named BtSY2) and BANAL-20-52 are phylogenetically closely related to SARS-CoV-2. Particularly, CX1 is the first SARS-CoV-2-related CoV containing Y501 in its receptor-binding domain (RBD) of the spike (S) protein. This study evaluated the interspecies transmission potential of the two CoVs and structurally elucidated the interplay between two RBD residues 498 and 501 on ACE2 binding, further highlighting the importance of surveillance on zoonotic CoVs.

PubMed: 40637421
DOI: 10.1128/jvi.00283-25

Experimental method

ELECTRON MICROSCOPY (2.74 Å)