2K2J

NMR solution structure of the split PH domain from Phospholipase C gamma 2

2K2J の概要

• エントリーDOI: 10.2210/pdb2k2j/pdb
• NMR情報: BMRB: 15707
• 分子名称: 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-2 (1 entity in total)
• 機能のキーワード: two sheeted beta barrel, c-terminal helix, calcium, hydrolase, lipid degradation, phosphoprotein, polymorphism, sh2 domain, sh3 domain, transducer, signaling protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14246.83

構造登録者

Harris, R.,Bunney, T.D.,Katan, M.,Driscoll, P.C. (登録日: 2008-04-02, 公開日: 2008-09-09, 最終更新日: 2024-05-01)

主引用文献

Walliser, C.,Retlich, M.,Harris, R.,Everett, K.L.,Josephs, M.B.,Vatter, P.,Esposito, D.,Driscoll, P.C.,Katan, M.,Gierschik, P.,Bunney, T.D.
Rac Regulates Its Effector Phospholipase C{gamma}2 through Interaction with a Split Pleckstrin Homology Domain.
J.Biol.Chem., 283:30351-30362, 2008

PubMed Abstract: Several isoforms of phospholipase C (PLC) are regulated through interactions with Ras superfamily GTPases, including Rac proteins. Interestingly, of two closely related PLCgamma isoforms, only PLCgamma(2) has previously been shown to be activated by Rac. Here, we explore the molecular basis of this interaction as well as the structural properties of PLCgamma(2) required for activation. Based on reconstitution experiments with isolated PLCgamma variants and Rac2, we show that an unusual pleckstrin homology (PH) domain, designated as the split PH domain (spPH), is both necessary and sufficient to effect activation of PLCgamma(2) by Rac2. We also demonstrate that Rac2 directly binds to PLCgamma(2) as well as to the isolated spPH of this isoform. Furthermore, through the use of NMR spectroscopy and mutational analysis, we determine the structure of spPH, define the structural features of spPH required for Rac interaction, and identify critical amino acid residues at the interaction interface. We further discuss parallels and differences between PLCgamma(1) and PLCgamma(2) and the implications of our findings for their respective signaling roles.

PubMed: 18728011
DOI: 10.1074/jbc.M803316200

実験手法

SOLUTION NMR