8ECQ

Bovine Fab 2G3

8ECQ の概要

• エントリーDOI: 10.2210/pdb8ecq/pdb
• 分子名称: 2G3 Fab Light chain, 2G3 Fab Heavy chain, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: antibody, immune system
• 由来する生物種: Bos taurus (cattle); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51242.74

構造登録者

Stanfield, R.L.,Wilson, I.A. (登録日: 2022-09-02, 公開日: 2023-09-20, 最終更新日: 2024-10-23)

主引用文献

Huang, R.,Warner Jenkins, G.,Kim, Y.,Stanfield, R.L.,Singh, A.,Martinez-Yamout, M.,Kroon, G.J.,Torres, J.L.,Jackson, A.M.,Kelley, A.,Shaabani, N.,Zeng, B.,Bacica, M.,Chen, W.,Warner, C.,Radoicic, J.,Joh, J.,Dinali Perera, K.,Sang, H.,Kim, T.,Yao, J.,Zhao, F.,Sok, D.,Burton, D.R.,Allen, J.,Harriman, W.,Mwangi, W.,Chung, D.,Teijaro, J.R.,Ward, A.B.,Dyson, H.J.,Wright, P.E.,Wilson, I.A.,Chang, K.O.,McGregor, D.,Smider, V.V.
The smallest functional antibody fragment: Ultralong CDR H3 antibody knob regions potently neutralize SARS-CoV-2.
Proc.Natl.Acad.Sci.USA, 120:e2303455120-e2303455120, 2023

PubMed Abstract: Cows produce antibodies with a disulfide-bonded antigen-binding domain embedded within ultralong heavy chain third complementarity determining regions. This "knob" domain is analogous to natural cysteine-rich peptides such as knottins in that it is small and stable but can accommodate diverse loops and disulfide bonding patterns. We immunized cattle with SARS-CoV-2 spike and found ultralong CDR H3 antibodies that could neutralize several viral variants at picomolar IC potencies in vitro and could protect from disease in vivo. The independent CDR H3 peptide knobs were expressed and maintained the properties of the parent antibodies. The knob interaction with SARS-CoV-2 spike was revealed by electron microscopy, X-ray crystallography, NMR spectroscopy, and mass spectrometry and established ultralong CDR H3-derived knobs as the smallest known recombinant independent antigen-binding fragment. Unlike other vertebrate antibody fragments, these knobs are not reliant on the immunoglobulin domain and have potential as a new class of therapeutics.

PubMed: 37722054
DOI: 10.1073/pnas.2303455120

実験手法

X-RAY DIFFRACTION (2 Å)