8YZC

Structure of BA.2.86 spike protein in complex with ACE2.

8YZC の概要

• エントリーDOI: 10.2210/pdb8yzc/pdb
• EMDBエントリー: 39689
• 分子名称: Spike glycoprotein,Fibritin,Expression Tag, Angiotensin-converting enzyme 2 (2 entities in total)
• 機能のキーワード: ace2, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 686163.54

構造登録者

Wang, Y.J.,Zang, X.,Sun, L. (登録日: 2024-04-06, 公開日: 2025-01-22, 最終更新日: 2025-07-16)

主引用文献

Liu, Y.,Zhao, X.,Shi, J.,Wang, Y.,Liu, H.,Hu, Y.F.,Hu, B.,Shuai, H.,Yuen, T.T.,Chai, Y.,Liu, F.,Gong, H.R.,Li, J.,Wang, X.,Jiang, S.,Zhang, X.,Zhang, Y.,Li, X.,Wang, L.,Hartnoll, M.,Zhu, T.,Hou, Y.,Huang, X.,Yoon, C.,Wang, Y.,He, Y.,Zhou, M.,Du, L.,Zhang, X.,Chan, W.M.,Chen, L.L.,Cai, J.P.,Yuan, S.,Zhou, J.,Huang, J.D.,Yuen, K.Y.,To, K.K.,Chan, J.F.,Zhang, B.Z.,Sun, L.,Wang, P.,Chu, H.
Lineage-specific pathogenicity, immune evasion, and virological features of SARS-CoV-2 BA.2.86/JN.1 and EG.5.1/HK.3.
Nat Commun, 15:8728-8728, 2024

PubMed Abstract: SARS-CoV-2 JN.1 with an additional L455S mutation on spike when compared with its parental variant BA.2.86 has outcompeted all earlier variants to become the dominant circulating variant. Recent studies investigated the immune resistance of SARS-CoV-2 JN.1 but additional factors are speculated to contribute to its global dominance, which remain elusive until today. Here, we find that SARS-CoV-2 JN.1 has a higher infectivity than BA.2.86 in differentiated primary human nasal epithelial cells (hNECs). Mechanistically, we demonstrate that the gained infectivity of SARS-CoV-2 JN.1 over BA.2.86 associates with increased entry efficiency conferred by L455S and better spike cleavage in hNECs. Structurally, S455 altered the mode of binding of JN.1 spike protein to ACE2 when compared to BA.2.86 spike at ACE2, and modified the internal structure of JN.1 spike protein by increasing the number of hydrogen bonds with neighboring residues. These findings indicate that a single mutation (L455S) enhances virus entry in hNECs and increases immune evasiveness, which contribute to the robust transmissibility of SARS-CoV-2 JN.1. We further evaluate the in vitro and in vivo virological characteristics between SARS-CoV-2 BA.2.86/JN.1 and EG.5.1/HK.3, and identify key lineage-specific features of the two Omicron sublineages that contribute to our understanding on Omicron antigenicity, transmissibility, and pathogenicity.

PubMed: 39379369
DOI: 10.1038/s41467-024-53033-7

実験手法

ELECTRON MICROSCOPY (2.7 Å)