8ZC5

SARS-CoV-2 Omicron BA.4 spike trimer (6P) in complex with D1F6 Fab, focused refinement of RBD region

8ZC5 の概要

• エントリーDOI: 10.2210/pdb8zc5/pdb
• EMDBエントリー: 39923
• 分子名称: Spike protein S1, Light chain of D1F6 Fab, Heavy chain of D1F6 Fab, ... (4 entities in total)
• 機能のキーワード: spike protein, antibody fab fragment, complex, viral protein/immune system, viral protein-immune system complex
• 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: 96297.58

構造登録者

Liu, B.,Gao, X.,Li, Z.,Chen, Q.,He, J.,Xiong, X. (登録日: 2024-04-28, 公開日: 2024-05-15, 最終更新日: 2024-11-13)

主引用文献

Liu, B.,Niu, X.,Deng, Y.,Zhang, Z.,Wang, Y.,Gao, X.,Liang, H.,Li, Z.,Wang, Q.,Cheng, Y.,Chen, Q.,Huang, S.,Pan, Y.,Su, M.,Lin, X.,Niu, C.,Chen, Y.,Yang, W.,Zhang, Y.,Yan, Q.,He, J.,Zhao, J.,Chen, L.,Xiong, X.
An unconventional VH1-2 antibody tolerates escape mutations and shows an antigenic hotspot on SARS-CoV-2 spike.
Cell Rep, 43:114265-114265, 2024

PubMed Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein continues to evolve antigenically, impacting antibody immunity. D1F6, an affinity-matured non-stereotypic VH1-2 antibody isolated from a patient infected with the SARS-CoV-2 ancestral strain, effectively neutralizes most Omicron variants tested, including XBB.1.5. We identify that D1F6 in the immunoglobulin G (IgG) form is able to overcome the effect of most Omicron mutations through its avidity-enhanced multivalent S-trimer binding. Cryo-electron microscopy (cryo-EM) and biochemical analyses show that three simultaneous epitope mutations are generally needed to substantially disrupt the multivalent S-trimer binding by D1F6 IgG. Antigenic mutations at spike positions 346, 444, and 445, which appeared in the latest variants, have little effect on D1F6 binding individually. However, these mutations are able to act synergistically with earlier Omicron mutations to impair neutralization by affecting the interaction between D1F6 IgG and the S-trimer. These results provide insight into the mechanism by which accumulated antigenic mutations facilitate evasion of affinity-matured antibodies.

PubMed: 38805396
DOI: 10.1016/j.celrep.2024.114265

実験手法

ELECTRON MICROSCOPY (3.91 Å)