6BU0

Crystal structure of the PI3KC2alpha C2 domain in complex with IP6

6BU0 の概要

• エントリーDOI: 10.2210/pdb6bu0/pdb
• 関連するPDBエントリー: 2B3R 6BTY 6BTZ
• 分子名称: Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha, FORMIC ACID, INOSITOL HEXAKISPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: c2 domain, lipid binding, phosphoinositide, pi3-kinase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 47750.93

構造登録者

Chen, K.-E.,Collins, B.M. (登録日: 2017-12-08, 公開日: 2018-10-17, 最終更新日: 2023-10-04)

主引用文献

Chen, K.E.,Tillu, V.A.,Chandra, M.,Collins, B.M.
Molecular Basis for Membrane Recruitment by the PX and C2 Domains of Class II Phosphoinositide 3-Kinase-C2 alpha.
Structure, 26:1612-, 2018

PubMed Abstract: Phosphorylation of phosphoinositides by the class II phosphatidylinositol 3-kinase (PI3K) PI3K-C2α is essential for many processes, including neuroexocytosis and formation of clathrin-coated vesicles. A defining feature of the class II PI3Ks is a C-terminal module composed of phox-homology (PX) and C2 membrane interacting domains; however, the mechanisms that control their specific cellular localization remain poorly understood. Here we report the crystal structure of the C2 domain of PI3K-C2α in complex with the phosphoinositide head-group mimic inositol hexaphosphate, revealing two distinct pockets for membrane binding. The C2 domain preferentially binds to phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate, and low-resolution structures of the combined PX-C2 module by small-angle X-ray scattering reveal a compact conformation in which cooperative lipid binding by each domain binding can occur. Finally, we demonstrate an unexpected role for calcium in perturbing the membrane interactions of the PX-C2 module, which we speculate may be important for regulating the activity of PI3K-C2α.

PubMed: 30293811
DOI: 10.1016/j.str.2018.08.010

実験手法

X-RAY DIFFRACTION (2.427 Å)