4BKL

Crystal structure of the arthritogenic antibody M2139 (Fab fragment) in complex with the triple-helical J1 peptide

4BKL の概要

• エントリーDOI: 10.2210/pdb4bkl/pdb
• 分子名称: M2139 FAB FRAGMENT HEAVY CHAIN, M2139 FAB FRAGMENT LIGHT CHAIN, J1 EPITOPE (3 entities in total)
• 機能のキーワード: immune system, antibody, rheumatoid arthritis, collagen type ii
• 由来する生物種: MUS MUSCULUS (HOUSE MOUSE); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 58596.88

構造登録者

Raposo, B.,Dobritzsch, D.,Ge, C.,Ekman, D.,Lindh, I.,Foerster, M.,Uysal, H.,Schneider, G.,Holmdahl, R. (登録日: 2013-04-26, 公開日: 2014-02-05, 最終更新日: 2023-12-20)

主引用文献

Raposo, B.,Dobritzsch, D.,Ge, C.,Ekman, D.,Xu, B.,Lindh, I.,Forster, M.,Uysal, H.,Nandakumar, K.S.,Schneider, G.,Holmdahl, R.
Epitope-Specific Antibody Response is Controlled by Immunoglobulin Vh Polymorphisms.
J.Exp.Med., 211:405-, 2014

PubMed Abstract: Autoantibody formation is essential for the development of certain autoimmune diseases like rheumatoid arthritis (RA). Anti-type II collagen (CII) antibodies are found in RA patients; they interact with cartilage in vivo and are often highly pathogenic in the mouse. Autoreactivity to CII is directed to multiple epitopes and conserved between mice and humans. We have previously mapped the antibody response to CII in a heterogeneous stock cohort of mice, with a strong association with the IgH locus. We positioned the genetic polymorphisms and determined the structural requirements controlling antibody recognition of one of the major CII epitopes. Polymorphisms at positions S31R and W33T of the associated variable heavy chain (VH) allele were identified and confirmed by gene sequencing. The Fab fragment binding the J1 epitope was crystallized, and site-directed mutagenesis confirmed the importance of those two variants for antigen recognition. Back mutation to germline sequence provided evidence for a preexisting recognition of the J1 epitope. These data demonstrate a genetic association of epitope-specific antibody responses with specific VH alleles, and it highlights the importance of germline-encoded antibodies in the pathogenesis of antibody-mediated autoimmune diseases.

PubMed: 24534192
DOI: 10.1084/JEM.20130968

実験手法

X-RAY DIFFRACTION (3.25 Å)