8G1C

Crystal structure of polyreactive 3B03 human Fab

8G1C の概要

• エントリーDOI: 10.2210/pdb8g1c/pdb
• 分子名称: Heavy chain of monoreactive 3B03 human Fab fragment, Light chain of monoreactive 3B03 human Fab fragment (3 entities in total)
• 機能のキーワード: immunoglobulin g, anti-influenza, monoreactive, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 93013.48

構造登録者

Borowska, M.T.,Adams, E.J. (登録日: 2023-02-01, 公開日: 2023-10-18, 最終更新日: 2024-10-23)

主引用文献

Borowska, M.T.,Boughter, C.T.,Bunker, J.J.,Guthmiller, J.J.,Wilson, P.C.,Roux, B.,Bendelac, A.,Adams, E.J.
Biochemical and biophysical characterization of natural polyreactivity in antibodies.
Cell Rep, 42:113190-113190, 2023

PubMed Abstract: To become specialized binders, antibodies undergo a process called affinity maturation to maximize their binding affinity. Despite this process, some antibodies retain low-affinity binding to diverse epitopes in a phenomenon called polyreactivity. Here we seek to understand the molecular basis of this polyreactivity in antibodies. Our results highlight that polyreactive antigen-binding fragments (Fabs) bind their targets with low affinities, comparable to T cell receptor recognition of autologous classical major histocompatibility complex. Extensive mutagenic studies find no singular amino acid residue or biochemical property responsible for polyreactive interaction, suggesting that polyreactive antibodies use multiple strategies for engagement. Finally, our crystal structures and all-atom molecular dynamics simulations of polyreactive Fabs show increased rigidity compared to their monoreactive relatives, forming a neutral and accessible platform for diverse antigens to bind. Together, these data support a cooperative strategy of rigid neutrality in establishing the polyreactive status of an antibody molecule.

PubMed: 37804505
DOI: 10.1016/j.celrep.2023.113190

実験手法

X-RAY DIFFRACTION (1.63 Å)