8T22

Cryo-EM structure of mink variant Y453F trimeric spike protein bound to one mink ACE2 receptors at downRBD conformation

This is a non-PDB format compatible entry.

Summary for 8T22

• Entry DOI: 10.2210/pdb8t22/pdb
• EMDB information: 40978
• Descriptor: Spike glycoprotein, Angiotensin-converting enzyme (2 entities in total)
• Functional Keywords: coronavirus, spike, ace2, mink, protein binding, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 4
• Total formula weight: 510107.83

Authors

Ahn, H.M.,Calderon, B.,Fan, X.,Gao, Y.,Horgan, N.,Zhou, B.,Liang, B. (deposition date: 2023-06-05, release date: 2023-10-25, Last modification date: 2024-10-23)

Primary citation

Ahn, H.,Calderon, B.M.,Fan, X.,Gao, Y.,Horgan, N.L.,Jiang, N.,Blohm, D.S.,Hossain, J.,Rayyan, N.W.K.,Osman, S.H.,Lin, X.,Currier, M.,Steel, J.,Wentworth, D.E.,Zhou, B.,Liang, B.
Structural basis of the American mink ACE2 binding by Y453F trimeric spike glycoproteins of SARS-CoV-2.
J Med Virol, 95:e29163-e29163, 2023

PubMed Abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2). While evolutionarily conserved, ACE2 receptors differ across various species and differential interactions with Spike (S) glycoproteins of SARS-CoV-2 viruses impact species specificity. Reverse zoonoses led to SARS-CoV-2 outbreaks on multiple American mink (Mustela vison) farms during the pandemic and gave rise to mink-associated S substitutions known for transmissibility between mink and zoonotic transmission to humans. In this study, we used bio-layer interferometry (BLI) to discern the differences in binding affinity between multiple human and mink-derived S glycoproteins of SARS-CoV-2 and their respective ACE2 receptors. Further, we conducted a structural analysis of a mink variant S glycoprotein and American mink ACE2 (mvACE2) using cryo-electron microscopy (cryo-EM), revealing four distinct conformations. We discovered a novel intermediary conformation where the mvACE2 receptor is bound to the receptor-binding domain (RBD) of the S glycoprotein in a "down" position, approximately 34° lower than previously reported "up" RBD. Finally, we compared residue interactions in the S-ACE2 complex interface of S glycoprotein conformations with varying RBD orientations. These findings provide valuable insights into the molecular mechanisms of SARS-CoV-2 entry.

PubMed: 37842796
DOI: 10.1002/jmv.29163

Experimental method

ELECTRON MICROSCOPY (3.83 Å)