EMD-41143
Cryo-EM structure of mink variant Y453F trimeric spike protein bound to one mink ACE2 receptors
EMD-41143
Single-particle3.75 Å
Deposition: 28/06/2023Map released: 25/10/2023
Last modified: 06/11/2024
Sample Organism:
Severe acute respiratory syndrome coronavirus 2,
Neogale vison
Sample: Cryo-EM structure of mink variant Y453F trimeric spike protein bound to two mink ACE2 receptors
Fitted models: 8taz (Avg. Q-score: 0.3)
Deposition Authors: Ahn HM, Calderon B, Fan X, Gao Y, Horgan N, Liang B
Sample: Cryo-EM structure of mink variant Y453F trimeric spike protein bound to two mink ACE2 receptors
Fitted models: 8taz (Avg. Q-score: 0.3)
Deposition Authors: Ahn HM, Calderon B, Fan X, Gao Y, Horgan N, Liang B
Structural basis of the American mink ACE2 binding by Y453F trimeric spike glycoproteins of SARS-CoV-2.
Ahn H,
Calderon BM,
Fan X,
Gao Y,
Horgan NL,
Jiang N ,
Blohm DS,
Hossain J,
Rayyan NWK,
Osman SH,
Lin X,
Currier M,
Steel J,
Wentworth DE,
Zhou B,
Liang B
(2023) J Med Virol , 95 , e29163 - e29163
,
Blohm DS,
Hossain J,
Rayyan NWK,
Osman SH,
Lin X,
Currier M,
Steel J,
Wentworth DE,
Zhou B,
Liang B
(2023) J Med Virol , 95 , e29163 - e29163
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.
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.