1DBM

MOLECULAR BASIS OF CROSS-REACTIVITY AND THE LIMITS OF ANTIBODY-ANTIGEN COMPLEMENTARITY

1DBM の概要

• エントリーDOI: 10.2210/pdb1dbm/pdb
• 分子名称: IGG1-KAPPA DB3 FAB (LIGHT CHAIN), IGG1-KAPPA DB3 FAB (HEAVY CHAIN), PROGESTERONE-11-ALPHA-OL-HEMISUCCINATE (3 entities in total)
• 機能のキーワード: immunoglobulin
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48065.78

構造登録者

Arevalo, J.H.,Wilson, I.A. (登録日: 1993-08-24, 公開日: 1994-01-31, 最終更新日: 2024-06-05)

主引用文献

Arevalo, J.H.,Taussig, M.J.,Wilson, I.A.
Molecular basis of crossreactivity and the limits of antibody-antigen complementarity.
Nature, 365:859-863, 1993

PubMed Abstract: Two major unanswered questions concerning the specificity of antibodies are: how do structurally different antigens bind with high affinity to the same antibody, and what are the limits of the antibody combining site complementarity and flexibility that contribute to such crossreactivity? We report here a comparative analysis of the X-ray structures of five conformationally different steroids in complex with the Fab' fragment of an anti-progesterone antibody DB3 at 2.7 A. This antibody is unable to complement completely the shape of the hydrophobic antigen so that crossreactivity occurs with other ligands without major structural rearrangements of the binding site. Antigen specificity can be explained through conserved interactions of DB3 with the steroid D-ring, whereas some of the crossreactivity is realized through different binding orientations of the steroid skeleton that place the A-ring into alternative pockets on the antibody surface. The restricted gene usage of the VGAM3.8 family in the generation of anti-progesterone monoclonal antibodies may be explained by the specific interaction of VH hallmark residues with the steroid D-ring. This first detailed structure of steroid interactions with a protein could be applied to the understanding of general mechanisms of steroid recognition as well as in the design of specific binding sites for small hydrophobic ligands.

PubMed: 8413674
DOI: 10.1038/365859a0

実験手法

X-RAY DIFFRACTION (2.7 Å)