5VJO

Complex between HyHEL10 Fab fragment heavy chain mutant I29F and Pekin duck egg lysozyme isoform I (DEL-I)

5VJO の概要

• エントリーDOI: 10.2210/pdb5vjo/pdb
• 関連するPDBエントリー: 5VJQ
• 分子名称: HyHEL10 heavy chain Fab fragment carrying I29F mutation., HyHEL10 light chain Fab fragment, lysozyme isoform I (DEL-I), ... (6 entities in total)
• 機能のキーワード: lysozyme, hydrolase, hydrolase-immune system complex, hydrolase/immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 121777.72

構造登録者

Langley, D.B.,Christ, D. (登録日: 2017-04-19, 公開日: 2018-04-11, 最終更新日: 2024-10-09)

主引用文献

Burnett, D.L.,Langley, D.B.,Schofield, P.,Hermes, J.R.,Chan, T.D.,Jackson, J.,Bourne, K.,Reed, J.H.,Patterson, K.,Porebski, B.T.,Brink, R.,Christ, D.,Goodnow, C.C.
Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination.
Science, 360:223-226, 2018

PubMed Abstract: Antibodies have the specificity to differentiate foreign antigens that mimic self antigens, but it remains unclear how such specificity is acquired. In a mouse model, we generated B cells displaying an antibody that cross-reacts with two related protein antigens expressed on self versus foreign cells. B cell anergy was imposed by self antigen but reversed upon challenge with high-density foreign antigen, leading to germinal center recruitment and antibody gene hypermutation. Single-cell analysis detected rapid selection for mutations that decrease self affinity and slower selection for epistatic mutations that specifically increase foreign affinity. Crystal structures revealed that these mutations exploited subtle topological differences to achieve 5000-fold preferential binding to foreign over self epitopes. Resolution of antigenic mimicry drove the optimal affinity maturation trajectory, highlighting the value of retaining self-reactive clones as substrates for protective antibody responses.

PubMed: 29650674
DOI: 10.1126/science.aao3859

実験手法

X-RAY DIFFRACTION (2.43 Å)