3A8P

Crystal structure of the Tiam2 PHCCEx domain

3A8P の概要

• エントリーDOI: 10.2210/pdb3a8p/pdb
• 関連するPDBエントリー: 3A8N 3A8Q
• 分子名称: T-lymphoma invasion and metastasis-inducing protein 2 (2 entities in total)
• 機能のキーワード: guanine nucleotide exchange factor, alternative splicing, cell projection, coiled coil, cytoplasm, guanine-nucleotide releasing factor, lipoprotein, myristate, phosphoprotein, signaling protein
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cytoplasm: Q6ZPF3
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 119702.87

構造登録者

Terawaki, S.,Kitano, K.,Mori, T.,Zhai, Y.,Higuchi, Y.,Itoh, N.,Watanabe, T.,Kaibuchi, K.,Hakoshima, T. (登録日: 2009-10-07, 公開日: 2009-11-24, 最終更新日: 2023-11-01)

主引用文献

Terawaki, S.,Kitano, K.,Mori, T.,Zhai, Y.,Higuchi, Y.,Itoh, N.,Watanabe, T.,Kaibuchi, K.,Hakoshima, T.
The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding module
Embo J., 29:236-250, 2010

PubMed Abstract: Tiam1 and Tiam2 (Tiam1/2) are guanine nucleotide-exchange factors that possess the PH-CC-Ex (pleckstrin homology, coiled coil and extra) region that mediates binding to plasma membranes and signalling proteins in the activation of Rac GTPases. Crystal structures of the PH-CC-Ex regions revealed a single globular domain, PHCCEx domain, comprising a conventional PH subdomain associated with an antiparallel coiled coil of CC subdomain and a novel three-helical globular Ex subdomain. The PH subdomain resembles the beta-spectrin PH domain, suggesting non-canonical phosphatidylinositol binding. Mutational and binding studies indicated that CC and Ex subdomains form a positively charged surface for protein binding. We identified two unique acidic sequence motifs in Tiam1/2-interacting proteins for binding to PHCCEx domain, Motif-I in CD44 and ephrinB's and the NMDA receptor, and Motif-II in Par3 and JIP2. Our results suggest the molecular basis by which the Tiam1/2 PHCCEx domain facilitates dual binding to membranes and signalling proteins.

PubMed: 19893486
DOI: 10.1038/emboj.2009.323

実験手法

X-RAY DIFFRACTION (2.1 Å)