4K2P

The Structure of a Quintuple Mutant of the Tiam1 PH-CC-Ex Domain

4K2P の概要

• エントリーDOI: 10.2210/pdb4k2p/pdb
• 関連するPDBエントリー: 4K2O
• 分子名称: T-lymphoma invasion and metastasis-inducing protein 1, CALCIUM ION (3 entities in total)
• 機能のキーワード: ph and coiled coil domain, phosphoinositide binding; protein-protein interaction, par-3, tight junctions, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell junction: Q13009
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 124855.80

構造登録者

Joshi, M.,Gakhar, L.,Fuentes, E.J. (登録日: 2013-04-09, 公開日: 2013-07-10, 最終更新日: 2023-09-20)

主引用文献

Joshi, M.,Gakhar, L.,Fuentes, E.J.
High-resolution structure of the Tiam1 PHn-CC-Ex domain.
Acta Crystallogr.,Sect.F, 69:744-752, 2013

PubMed Abstract: The T-lymphoma and metastasis gene 1 (TIAM1) encodes a guanine nucleotide-exchange factor protein (Tiam1) that is specific for the Rho-family GTPase Rac1 and is important for cell polarity, migration and adhesion. Tiam1 is a large multi-domain protein that contains several protein-protein binding domains that are important for regulating cellular function. The PHn-CC-Ex domain is critical for plasma-membrane association and interactions with protein-scaffold proteins (e.g. Par3b, spinophilin, IRSp53 and JIP2) that direct Tiam1-Rac1 signaling specificity. It was determined that the coiled-coil domain of Par3b binds the PHn-CC-Ex domain with a dissociation constant of ≈ 30 µM. Moreover, the structures of two variants of the Tiam1 PHn-CC-Ex domain were solved at resolutions of 1.98 and 2.15 Å, respectively. The structures indicate that the PHn, CC and Ex regions form independent subdomains that together provide an integrated platform for binding partner proteins. Small-angle X-ray scattering (SAXS) data indicate that the Tiam1 PHn-CC-Ex domain is monomeric in solution and that the solution and crystal structures are very similar. Together, these data provide the foundation necessary to elucidate the structural mechanism of the PHn-CC-Ex/scaffold interactions that are critical for Tiam1-Rac1 signaling specificity.

PubMed: 23832200
DOI: 10.1107/S1744309113014206

実験手法

X-RAY DIFFRACTION (1.98 Å)