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-Structure paper
タイトル | Structural basis of the American mink ACE2 binding by Y453F trimeric spike glycoproteins of SARS-CoV-2. |
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ジャーナル・号・ページ | J Med Virol, Vol. 95, Issue 10, Page e29163, Year 2023 |
掲載日 | 2023-10-?? |
著者 | Hyunjun Ahn / Brenda M Calderon / Xiaoyu Fan / Yunrong Gao / Natalie L Horgan / Nannan Jiang / Dylan S Blohm / Jaber Hossain / Nicole Wedad K Rayyan / Sarah H Osman / Xudong Lin / Michael Currier / John Steel / David E Wentworth / Bin Zhou / Bo Liang / |
PubMed 要旨 | 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 ...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. |
リンク | J Med Virol / PubMed:37842796 |
手法 | EM (単粒子) |
解像度 | 3.36 - 3.87 Å |
構造データ | EMDB-40976, PDB-8t20: EMDB-40977, PDB-8t21: EMDB-40978, PDB-8t22: EMDB-40979, PDB-8t23: EMDB-40980, PDB-8t25: EMDB-41143, PDB-8taz: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN (ウイルスタンパク質) / Coronavirus (オルトコロナウイルス亜科) / Spike / ACE2 (アンジオテンシン変換酵素2) / Mink / Protein binding (タンパク質) / SARS-CoV-2 (SARSコロナウイルス2) |