2P4R

Structural basis for a novel interaction between AIP4 and beta-PIX

2P4R の概要

• エントリーDOI: 10.2210/pdb2p4r/pdb
• 関連するPDBエントリー: 2AK5 2DF6 2G6F
• 分子名称: Rho guanine nucleotide exchange factor 7, E3 ubiquitin-protein ligase Itchy homolog, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: sh3 domain peptide ligand complex, ligase
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• 細胞内の位置: Cell membrane: Q96J02
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 9617.63

構造登録者

Min, K.C. (登録日: 2007-03-13, 公開日: 2007-07-24, 最終更新日: 2023-08-30)

主引用文献

Janz, J.M.,Sakmar, T.P.,Min, K.C.
A novel interaction between atrophin-interacting protein 4 and beta-p21-activated kinase-interactive exchange factor is mediated by an SH3 domain.
J.Biol.Chem., 282:28893-28903, 2007

PubMed Abstract: Cross-talk between G protein-coupled receptors and receptor tyrosine kinase signaling pathways is crucial to the efficient relay and integration of cellular information. Here we identify and define the novel binding interaction of the E3 ubiquitin ligase atrophin-interacting protein 4 (AIP4) with the GTP exchange factor beta-p21-activated kinase-interactive exchange factor (beta PIX). We demonstrate that this interaction is mediated in part by the beta PIX-SH3 domain binding to a proline-rich stretch of AIP4. Analysis of the interaction by isothermal calorimetry is consistent with a heterotrimeric complex with one AIP4-derived peptide binding to two beta PIX-SH3 domains. We determined the crystal structure of the beta PIX-SH3.AIP4 complex to 2.0-A resolution. In contrast to the calorimetry results, the crystal structure shows a monomeric complex in which AIP4 peptide binds the beta PIX-SH3 domain as a canonical Class I ligand with an additional type II polyproline helix that makes extensive contacts with another face of beta PIX. Taken together, the novel interaction between AIP4 and beta PIX represents a new regulatory node for G protein-coupled receptor and receptor tyrosine kinase signal integration. Our structure of the beta PIX-SH3.AIP4 complex provides important insight into the mechanistic basis for beta PIX scaffolding of signaling components, especially those involved in cross-talk.

PubMed: 17652093
DOI: 10.1074/jbc.M702678200

実験手法

X-RAY DIFFRACTION (2.001 Å)