2iwl

From Proteopedia

Revision as of 20:42, 12 November 2007

STRUCTURE OF THE PX DOMAIN OF PHOSPHOINOSITIDE 3-KINASE-C2ALPHA

Overview

Phox homology (PX) domains, which have been identified in a variety of, proteins involved in cell signaling and membrane trafficking, have been, shown to interact with phosphoinositides (PIs) with different affinities, and specificities. To elucidate the structural origin of diverse PI, specificities of PX domains, we determined the crystal structure of the PX, domain from phosphoinositide 3-kinase C2alpha (PI3K-C2alpha), which binds, phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)). To delineate the, mechanism by which this PX domain interacts with membranes, we measured, the membrane binding of the wild type domain and mutants by surface, plasmon resonance and monolayer techniques. This PX domain contains a, signature PI-binding site that is optimized for PtdIns(4,5)P(2) binding., The membrane binding of the PX domain is initiated by nonspecific, electrostatic interactions followed by the membrane penetration of, hydrophobic residues. Membrane penetration is specifically enhanced by, PtdIns(4,5)P(2). Furthermore, the PX domain displayed significantly higher, PtdIns(4,5)P(2) membrane affinity and specificity when compared with the, PI3K-C2alpha C2 domain, demonstrating that high affinity PtdIns(4,5)P(2), binding was facilitated by the PX domain in full-length PI3K-C2alpha., Together, these studies provide new structural insight into the diverse PI, specificities of PX domains and elucidate the mechanism by which the, PI3K-C2alpha PX domain interacts with PtdIns(4,5)P(2)-containing membranes, and thereby mediates the membrane recruitment of PI3K-C2alpha.

About this Structure

2IWL is a Single protein structure of sequence from Homo sapiens with SO4 as ligand. Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

Structural and membrane binding analysis of the Phox homology domain of phosphoinositide 3-kinase-C2alpha., Stahelin RV, Karathanassis D, Bruzik KS, Waterfield MD, Bravo J, Williams RL, Cho W, J Biol Chem. 2006 Dec 22;281(51):39396-406. Epub 2006 Oct 12. PMID:17038310

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