6BTZ

Crystal structure of the PI3KC2alpha C2 domain in space group C121

Summary for 6BTZ

• Entry DOI: 10.2210/pdb6btz/pdb
• Related: 2B3R
• Descriptor: Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha, SULFATE ION, 1,4,7,10,13,16-HEXAOXACYCLOOCTADECANE, ... (5 entities in total)
• Functional Keywords: c2 domain, lipid binding, phosphoinositide, pi3-kinase, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 63544.27

Authors

Chen, K.-E.,Collins, B.M. (deposition date: 2017-12-08, release date: 2018-10-17, Last modification date: 2023-10-04)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.85 Å)