4JG0

Structure of phosphoserine/threonine (pSTAb) scaffold bound to pSer peptide

4JG0 の概要

• エントリーDOI: 10.2210/pdb4jg0/pdb
• 関連するPDBエントリー: 4JFX 4JFY 4JFZ 4JG1
• 分子名称: Fab light chain, Fab heavy chain, Phosphopeptide, ... (5 entities in total)
• 機能のキーワード: immmunoglobulin domain, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 49814.39

構造登録者

Koerber, J.T.,Thomsen, N.D.,Hannigan, B.T.,Degrado, W.F.,Wells, J.A. (登録日: 2013-02-28, 公開日: 2013-08-28, 最終更新日: 2024-11-27)

主引用文献

Koerber, J.T.,Thomsen, N.D.,Hannigan, B.T.,Degrado, W.F.,Wells, J.A.
Nature-inspired design of motif-specific antibody scaffolds.
Nat.Biotechnol., 31:916-921, 2013

PubMed Abstract: Aberrant changes in post-translational modifications (PTMs) such as phosphate groups underlie a majority of human diseases. However, detection and quantification of PTMs for diagnostic or biomarker applications often require PTM-specific monoclonal antibodies (mAbs), which are challenging to generate using traditional antibody-selection methods. Here we outline a general strategy for producing synthetic, PTM-specific mAbs by engineering a motif-specific 'hot spot' into an antibody scaffold. Inspired by a natural phosphate-binding motif, we designed and selected mAb scaffolds with hot spots specific for phosphoserine, phosphothreonine or phosphotyrosine. Crystal structures of the phospho-specific mAbs revealed two distinct modes of phosphoresidue recognition. Our data suggest that each hot spot functions independently of the surrounding scaffold, as phage display antibody libraries using these scaffolds yielded >50 phospho- and target-specific mAbs against 70% of target peptides. Our motif-specific scaffold strategy may provide a general solution for rapid, robust development of anti-PTM mAbs for signaling, diagnostic and therapeutic applications.

PubMed: 23955275
DOI: 10.1038/nbt.2672

実験手法

X-RAY DIFFRACTION (1.81 Å)