5CJP

The Structural Basis for Cdc42-Induced Dimerization of IQGAPs

5CJP の概要

• エントリーDOI: 10.2210/pdb5cjp/pdb
• 分子名称: Cell division cycle 42 (GTP binding protein, 25kDa), isoform CRA_a, Ras GTPase-activating-like protein IQGAP2, GUANOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: iqgap2 gap related domain x-ray gtpase interactions complex cdc42, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 169341.12

構造登録者

Worthylake, D.K.,Boyapati, V.K.,LeCour Jr, L. (登録日: 2015-07-14, 公開日: 2016-08-10, 最終更新日: 2024-03-06)

主引用文献

LeCour, L.,Boyapati, V.K.,Liu, J.,Li, Z.,Sacks, D.B.,Worthylake, D.K.
The Structural Basis for Cdc42-Induced Dimerization of IQGAPs.
Structure, 24:1499-1508, 2016

PubMed Abstract: In signaling, Rho-family GTPases bind effector proteins and alter their behavior. Here we present the crystal structure of Cdc42·GTP bound to the GTPase-activating protein (GAP)-related domain (GRD) of IQGAP2. Four molecules of Cdc42 are bound to two GRD molecules, which bind each other in a parallel dimer. Two Cdc42s bind very similarly to the Ras/RasGAP interaction, while the other two bind primarily to "extra domain" sequences from both GRDs, tying the GRDs together. Calorimetry confirms two-site binding of Cdc42·GTP for the GRDs of both IQGAP2 and IQGAP1. Mutation of important extra domain residues reduces binding to single-site and abrogates Cdc42 binding to a much larger IQGAP1 fragment. Importantly, Rac1·GTP displays only single-site binding to the GRDs, indicating that only Cdc42 promotes IQGAP dimerization. The structure identifies an unexpected role for Cdc42 in protein dimerization, thus expanding the repertoire of interactions of Ras family proteins with their targets.

PubMed: 27524202
DOI: 10.1016/j.str.2016.06.016

実験手法

X-RAY DIFFRACTION (2.6 Å)