6J11

MERS-CoV spike N-terminal domain and 7D10 scFv complex

6J11 の概要

• エントリーDOI: 10.2210/pdb6j11/pdb
• 分子名称: N-terminal domain of Spike glycoprotein, VH of 7D10, VL of 7D10, ... (9 entities in total)
• 機能のキーワード: mers-cov, antibody, viral protein
• 由来する生物種: Middle East respiratory syndrome-related coronavirus; 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 203134.76

構造登録者

Zhou, H.,Zhang, S.,Zhang, S.,Tang, W.,Wang, X. (登録日: 2018-12-27, 公開日: 2019-07-24, 最終更新日: 2024-11-13)

主引用文献

Zhou, H.,Chen, Y.,Zhang, S.,Niu, P.,Qin, K.,Jia, W.,Huang, B.,Zhang, S.,Lan, J.,Zhang, L.,Tan, W.,Wang, X.
Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein.
Nat Commun, 10:3068-3068, 2019

PubMed Abstract: Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies.

PubMed: 31296843
DOI: 10.1038/s41467-019-10897-4

実験手法

X-RAY DIFFRACTION (3 Å)