8YZC
Structure of BA.2.86 spike protein in complex with ACE2.
Summary for 8YZC
Entry DOI | 10.2210/pdb8yzc/pdb |
EMDB information | 39689 |
Descriptor | Spike glycoprotein,Fibritin,Expression Tag, Angiotensin-converting enzyme 2 (2 entities in total) |
Functional Keywords | ace2, viral protein |
Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2) More |
Total number of polymer chains | 6 |
Total formula weight | 686163.54 |
Authors | |
Primary citation | 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 Cited by 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: 39379369DOI: 10.1038/s41467-024-53033-7 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (2.7 Å) |
Structure validation
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