3AWF

Crystal structure of Pten-like domain of Ci-VSP (236-576)

3AWF の概要

• エントリーDOI: 10.2210/pdb3awf/pdb
• 関連するPDBエントリー: 3AWE 3AWG
• 分子名称: Voltage-sensor containing phosphatase, SULFATE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: ptdins(3, 4, 5)p3, phosphatase, ion channel, hydrolase, membrane protein
• 由来する生物種: Ciona intestinalis (Transparent sea squirt)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 119678.09

構造登録者

Matsuda, M.,Sakata, S.,Takeshita, K.,Suzuki, M.,Yamashita, E.,Okamura, Y.,Nakagawa, A. (登録日: 2011-03-19, 公開日: 2011-05-04, 最終更新日: 2024-10-30)

主引用文献

Matsuda, M.,Takeshita, K.,Kurokawa, T.,Sakata, S.,Suzuki, M.,Yamashita, E.,Okamura, Y.,Nakagawa, A.
Crystal structure of the cytoplasmic phosphatase and tensin homolog (PTEN)-like region of Ciona intestinalis voltage-sensing phosphatase provides insight into substrate specificity and redox regulation of the phosphoinositide phosphatase activity
J.Biol.Chem., 286:23368-23377, 2011

PubMed Abstract: Ciona intestinalis voltage-sensing phosphatase (Ci-VSP) has a transmembrane voltage sensor domain and a cytoplasmic region sharing similarity to the phosphatase and tensin homolog (PTEN). It dephosphorylates phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate upon membrane depolarization. The cytoplasmic region is composed of a phosphatase domain and a putative membrane interaction domain, C2. Here we determined the crystal structures of the Ci-VSP cytoplasmic region in three distinct constructs, wild-type (248-576), wild-type (236-576), and G365A mutant (248-576). The crystal structure of WT-236 and G365A-248 had the disulfide bond between the catalytic residue Cys-363 and the adjacent residue Cys-310. On the other hand, the disulfide bond was not present in the crystal structure of WT-248. These suggest the possibility that Ci-VSP is regulated by reactive oxygen species as found in PTEN. These structures also revealed that the conformation of the TI loop in the active site of the Ci-VSP cytoplasmic region was distinct from the corresponding region of PTEN; Ci-VSP has glutamic acid (Glu-411) in the TI loop, orienting toward the center of active site pocket. Mutation of Glu-411 led to acquirement of increased activity toward phosphatidylinositol 3,5-bisphosphate, suggesting that this site is required for determining substrate specificity. Our results provide the basic information of the enzymatic mechanism of Ci-VSP.

PubMed: 21543329
DOI: 10.1074/jbc.M110.214361

実験手法

X-RAY DIFFRACTION (1.99 Å)