2K76

Solution structure of a paralog-specific Mena binder by NMR

2K76 の概要

• エントリーDOI: 10.2210/pdb2k76/pdb
• NMR情報: BMRB: 15946
• 分子名称: pGolemi (1 entity in total)
• 機能のキーワード: protein design, miniature protein, app, beta-hairpin, acta homolog, de novo protein
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3459.83

構造登録者

Link, N.M.,Hunke, C.,Eichler, J.,Bayer, P. (登録日: 2008-08-03, 公開日: 2009-06-16, 最終更新日: 2024-05-22)

主引用文献

Link, N.M.,Hunke, C.,Mueller, J.W.,Eichler, J.,Bayer, P.
The solution structure of pGolemi, a high affinity Mena EVH1 binding miniature protein, suggests explanations for paralog-specific binding to Ena/VASP homology (EVH) 1 domains.
Biol.Chem., 390:417-426, 2009

PubMed Abstract: Ena/VASP homology 1 (EVH1) domains are polyproline binding domains that are present in a wide range of adaptor proteins, among them Ena/VASP proteins involved in actin remodeling and axonal guidance. The interaction of ActA, a transmembrane protein from the food-borne pathogen Listeria monocytogenes, with EVH1 domains has been shown to be crucial for recruitment of the host's actin skeleton and, as a consequence, for the infectivity of this bacterium. We present the structure of a synthetic high-affinity Mena EVH1 ligand, pGolemi, capable of paralog-specific binding, solved by NMR spectroscopy. This peptide shares the common pancreatic peptide fold with its scaffold, avian pancreatic peptide, but shows pivotal differences in the amino-terminus. The interplay of spatial fixation and flexibility appears to be the reason for its high affinity towards Mena EVH1. Combined with earlier investigations, our structural data shed light on the specificity determinants of pGolemi and the importance of additional binding epitopes around the residues Thr74 and Phe32 on EVH1 domains regulating paralog specificity. Our results are expected to facilitate the design of other high-affinity, paralog-specific EVH1 domain ligands, and serve as a fundament for the investigation of the molecular mode of action of EVH1 domains.

PubMed: 19284291
DOI: 10.1515/BC.2009.045

実験手法

SOLUTION NMR