7EFR

Structure of SARS-CoV-2 spike receptor-binding domain in complex with high affinity ACE2 mutant (T27W,N330Y)

7EFR の概要

• エントリーDOI: 10.2210/pdb7efr/pdb
• 分子名称: Processed angiotensin-converting enzyme 2, Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: receptor-binding domain, angiotensin converting enzyme 2, viral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 94982.52

構造登録者

Lu, G.W.,Ye, F.,Lin, X. (登録日: 2021-03-23, 公開日: 2021-11-24, 最終更新日: 2024-10-16)

主引用文献

Ye, F.,Lin, X.,Chen, Z.,Yang, F.,Lin, S.,Yang, J.,Chen, H.,Sun, H.,Wang, L.,Wen, A.,Zhang, X.,Dai, Y.,Cao, Y.,Yang, J.,Shen, G.,Yang, L.,Li, J.,Wang, Z.,Wang, W.,Wei, X.,Lu, G.
S19W, T27W, and N330Y mutations in ACE2 enhance SARS-CoV-2 S-RBD binding toward both wild-type and antibody-resistant viruses and its molecular basis.
Signal Transduct Target Ther, 6:343-343, 2021

PubMed Abstract: SARS-CoV-2 recognizes, via its spike receptor-binding domain (S-RBD), human angiotensin-converting enzyme 2 (ACE2) to initiate infection. Ecto-domain protein of ACE2 can therefore function as a decoy. Here we show that mutations of S19W, T27W, and N330Y in ACE2 could individually enhance SARS-CoV-2 S-RBD binding. Y330 could be synergistically combined with either W19 or W27, whereas W19 and W27 are mutually unbeneficial. The structures of SARS-CoV-2 S-RBD bound to the ACE2 mutants reveal that the enhanced binding is mainly contributed by the van der Waals interactions mediated by the aromatic side-chains from W19, W27, and Y330. While Y330 and W19/W27 are distantly located and devoid of any steric interference, W19 and W27 are shown to orient their side-chains toward each other and to cause steric conflicts, explaining their incompatibility. Finally, using pseudotyped SARS-CoV-2 viruses, we demonstrate that these residue substitutions are associated with dramatically improved entry-inhibition efficacy toward both wild-type and antibody-resistant viruses. Taken together, our biochemical and structural data have delineated the basis for the elevated S-RBD binding associated with S19W, T27W, and N330Y mutations in ACE2, paving the way for potential application of these mutants in clinical treatment of COVID-19.

PubMed: 34531369
DOI: 10.1038/s41392-021-00756-4

実験手法

X-RAY DIFFRACTION (2.494 Å)