3IET

Crystal Structure of 237mAb with antigen

3IET の概要

• エントリーDOI: 10.2210/pdb3iet/pdb
• 関連するPDBエントリー: 3IF1
• 分子名称: Immunoglobulin light chain (IgG2a), Immunoglobulin heavy chain (IgG2a), Podoplanin, ... (6 entities in total)
• 機能のキーワード: glycopepitde, antibody, fab, carbohydrate-biding, tumour, 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: 97395.61

構造登録者

Brooks, C.L.,Evans, S.V.,Borisova, S.N. (登録日: 2009-07-23, 公開日: 2010-06-23, 最終更新日: 2024-11-06)

主引用文献

Brooks, C.L.,Schietinger, A.,Borisova, S.N.,Kufer, P.,Okon, M.,Hirama, T.,Mackenzie, C.R.,Wang, L.X.,Schreiber, H.,Evans, S.V.
Antibody recognition of a unique tumor-specific glycopeptide antigen.
Proc.Natl.Acad.Sci.USA, 107:10056-10061, 2010

PubMed Abstract: Aberrant glycosylation and the overexpression of certain carbohydrate moieties is a consistent feature of cancers, and tumor-associated oligosaccharides are actively investigated as targets for immunotherapy. One of the most common aberrations in glycosylation patterns is the presentation of a single O-linked N-acetylgalactosamine on a threonine or serine residue known as the "Tn antigen." Whereas the ubiquitous nature of Tn antigens on cancers has made them a natural focus of vaccine research, such carbohydrate moieties are not always tumor-specific and have been observed on embryonic and nonmalignant adult tissue. Here we report the structural basis of binding of a complex of a monoclonal antibody (237mAb) with a truly tumor-specific glycopeptide containing the Tn antigen. In contrast to glycopeptide-specific antibodies in complex with simple peptides, 237mAb does not recognize a conformational epitope induced in the peptide by sugar substitution. Instead, 237mAb uses a pocket coded by germ-line genes to completely envelope the carbohydrate moiety itself while interacting with the peptide moiety in a shallow groove. Thus, 237mAb achieves its striking tumor specificity, with no observed physiological cross-reactivity to the unglycosylated peptide or the free glycan, by a combination of multiple weak but specific interactions to both the peptide and to the glycan portions of the antigen.

PubMed: 20479270
DOI: 10.1073/pnas.0915176107

実験手法

X-RAY DIFFRACTION (2.2 Å)