3OJD

Anti-Indolicidin monoclonal antibody V2D2 (Fab fragment)

3OJD の概要

• エントリーDOI: 10.2210/pdb3ojd/pdb
• 分子名称: Fab V2D2 (3 entities in total)
• 機能のキーワード: beta-sandwich immunoglobulin fold, antigen binding, secreted protein, anti-indolicidin fab, surrogate receptor, immune system
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47814.22

構造登録者

Lomash, S.,Salunke, D.M. (登録日: 2010-08-22, 公開日: 2010-09-01, 最終更新日: 2024-11-13)

主引用文献

Lomash, S.,Nagpal, S.,Salunke, D.M.
An antibody as surrogate receptor reveals determinants of activity of an innate immune peptide antibiotic
J.Biol.Chem., 285:35750-35758, 2010

PubMed Abstract: Drug discovery initiatives often depend critically on knowledge of ligand-receptor interactions. However, the identity or structure of the target receptor may not be known in every instance. The concept of receptor surrogate, a molecular environment mimic of natural receptor, may prove beneficial under such circumstances. Here, we demonstrate the potential of monoclonal antibodies (mAbs) to act as surrogate receptors for a class of innate immune peptide antibiotics, a strategy that can help comprehend their action mechanism and identify chemical entities crucial for activity. A panel of antibody surrogates was raised against indolicidin, a tryptophan-rich cationic broad spectrum antimicrobial peptide of innate immune origin. Employing an elegant combination of thermodynamics, crystallography, and molecular modeling, interactions of the peptide with a high affinity anti-indolicidin monoclonal antibody were analyzed and were used to identify a motif that contained almost the entire antibiotic activity of native indolicidin. The analysis clarified the interaction of the peptide with previously proposed targets such as bacterial cell membrane and DNA and could further be correlated with antimicrobial compounds whose actions involve varied other mechanisms. These features suggest a multipronged assault pathway for indolicidin. Remarkably, the anti-indolicidin mAb surrogate was able to isolate additional independent bactericidal sequences from a random peptide library, providing compelling evidence as to the physiological relevance of surrogate receptor concept and suggesting applications in receptor-based pharmacophore research.

PubMed: 20837490
DOI: 10.1074/jbc.M110.150516

実験手法

X-RAY DIFFRACTION (2 Å)