1E4X

crossreactive binding of a circularized peptide to an anti-TGFalpha antibody Fab-fragment

1E4X の概要

• エントリーDOI: 10.2210/pdb1e4x/pdb
• 関連するPDBエントリー: 1E4W 1FBI
• 分子名称: TAB2, CYCLIC PEPTIDE, ... (5 entities in total)
• 機能のキーワード: immune system, complex (antibody-antigen), cross-reactivity, protein-peptide recognition
• 由来する生物種: MUS MUSCULUS (HOUSE MOUSE); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 95520.07

構造登録者

Hahn, M.,Winkler, D.,Misselwitz, R.,Wessner, H.,Welfle, K.,Zahn, G.,Schneider-Mergener, J.,Hoehne, W. (登録日: 2000-07-12, 公開日: 2001-07-12, 最終更新日: 2024-10-23)

主引用文献

Hahn, M.,Winkler, D.,Welfle, K.,Misselwitz, R.,Welfle, H.,Wessner, H.,Zahn, G.,Scholz, C.,Seifert, M.,Harkins, R.,Schneider-Mergener, J.,Hoehne, W.
Cross-Reactive Binding of Cyclic Peptides to an Anti-Tgf Alpha Antibody Fab Fragment: An X-Ray Structural and Thermodynamic Analysis
J.Mol.Biol., 314:293-, 2001

PubMed Abstract: The monoclonal antibody tAb2 binds the N-terminal sequence of transforming growth factor alpha, VVSHFND. With the help of combinatorial peptide libraries it is possible to find homologous peptides that bind tAb2 with an affinity similar to that of the epitope. The conformational flexibility of short peptides can be constrained by cyclization in order to improve their affinity to the antibody and their stability towards proteolysis. Two cyclic peptides which are cross-reactive binders for tAb2 were selected earlier using combinatorial peptide libraries. One is cyclized by an amide bond between the N-alpha group and the side-chain of the last residue (cyclo-SHFNEYE), and the other by a disulfide bridge (cyclo-CSHFNDYC). The complex structures of tAb2 with the linear epitope peptide VVSHFND and with cyclo-SHFNEYE were determined by X-ray diffraction. Both peptides show a similar conformation and binding pattern in the complex. The linear peptide SHFNEYE does not bind tAb2, but cyclo-SHFNEYE is stabilized in a loop conformation suitable for binding. Hence the cyclization counteracts the exchange of aspartate in the epitope sequence to glutamate. Isothermal titration calorimetry was used to characterize the binding energetics of tAb2 with the two cyclic peptides and the epitope peptide. The binding reactions are enthalpically driven with an unfavorable entropic contribution under all measured conditions. The association reactions are characterized by negative DeltaC(p) changes and by the uptake of one proton per binding site. A putative candidate for proton uptake during binding is the histidine residue in each of the peptides. Hydrogen bonds and the putative formation of an electrostatic pair between the protonated histidine and a carboxy group may contribute markedly to the favorable enthalpy of complex formation. Implications to cyclization of peptides for stabilization are discussed.

PubMed: 11718562
DOI: 10.1006/JMBI.2001.5135

実験手法

X-RAY DIFFRACTION (1.9 Å)