6P4B

HyHEL10 fab variant HyHEL10-4x (heavy chain mutations L4F, Y33H, S56N, and Y58F) bound to hen egg lysozyme variant HEL2x-flex (mutations R21Q, R73E, C76S, and C94S)

6P4B の概要

• エントリーDOI: 10.2210/pdb6p4b/pdb
• 分子名称: HyHEL10 Fab light chain, HyHEL10 Fab heavy chain, Lysozyme C, ... (5 entities in total)
• 機能のキーワード: hel2x-flex, hyhel10-4x, fab, antigen-antibody, hydrolase-immune system complex, hydrolase/immune system
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 124604.40

構造登録者

Langley, D.B.,Christ, D. (登録日: 2019-05-27, 公開日: 2020-05-27, 最終更新日: 2024-10-16)

主引用文献

Burnett, D.L.,Schofield, P.,Langley, D.B.,Jackson, J.,Bourne, K.,Wilson, E.,Porebski, B.T.,Buckle, A.M.,Brink, R.,Goodnow, C.C.,Christ, D.
Conformational diversity facilitates antibody mutation trajectories and discrimination between foreign and self-antigens.
Proc.Natl.Acad.Sci.USA, 117:22341-22350, 2020

PubMed Abstract: Conformational diversity and self-cross-reactivity of antigens have been correlated with evasion from neutralizing antibody responses. We utilized single cell B cell sequencing, biolayer interferometry and X-ray crystallography to trace mutation selection pathways where the antibody response must resolve cross-reactivity between foreign and self-proteins bearing near-identical contact surfaces, but differing in conformational flexibility. Recurring antibody mutation trajectories mediate long-range rearrangements of framework (FW) and complementarity determining regions (CDRs) that increase binding site conformational diversity. These antibody mutations decrease affinity for self-antigen 19-fold and increase foreign affinity 67-fold, to yield a more than 1,250-fold increase in binding discrimination. These results demonstrate how conformational diversity in antigen and antibody does not act as a barrier, as previously suggested, but rather facilitates high affinity and high discrimination between foreign and self.

PubMed: 32855302
DOI: 10.1073/pnas.2005102117

実験手法

X-RAY DIFFRACTION (1.9 Å)