4eza

Publication Abstract from PubMed

Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding module exemplified by select IQGAPs (IQ motif containing GTPase activating proteins) known to co-ordinate cellular signalling events and cytoskeletal dynamics. This module is defined by a C-terminal 105-107 amino acid region of which that from IQGAP1 and 2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP(3)). The binding affinity for PtdInsP(3), together with other, secondary target-recognition characteristics, are comparable to those of the pleckstrin homology (PH) domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP(3) effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 PH domain, each tagged with enhanced green fluorescent protein, both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signalling and constitutes a novel, atypical phosphoinositide (aPI) binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules.

IQGAP proteins reveal an atypical phosphoinositide (aPI) binding domain with a pseudo C2 domain fold.,Dixon MJ, Gray A, Schenning M, Agacan M, Tempel W, Tong Y, Nedyalkova L, Park HW, Leslie NR, van Aalten DM, Downes CP, Batty IH J Biol Chem. 2012 Apr 5. PMID:22493426^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.