Evidence suggests that PtdIns(3,4,5)P3 initiates down-stream signaling by recruiting and/or activating target proteins on the plasma membrane. Considering the presence of various phosphatidylinositol phosphates and other phospholipids in the membrane, selective recognition of PtdIns(3,4,5)P3 at the interface represents a crucial issue in addressing its mode of action. In this study, we took a novel approach to explore specific PtdIns(3,4,5)P, recognition by identifying a synthetic peptide WAAKIQASFRGHMARKK that displayed discriminative affinity with the D-3 phosphoinositide. It formed a 1:1 complex with PtdIns(3,4,5)P3 with Kd of 2 U.M, but bound PtdIns(4,5)P2 and PtdIns(3,4)P2 with substantially lower affinity despite the largely shared structural motifs. Several lines of evidence indicate that this phosphoinositide-peptide interaction is not caused by nonspecific electrostatic interactions or phospholipid aggregation, and requires a cooperative action among the hydrophobic and basic residues to exert the selective recognition. Moreover, we identified two internal peptide sequences that bear sequence homology to the binding peptide on the SH2 domains of the p85 subunit of phosphoinositide 3-kinase. Evidence suggests that these internal peptides may represent the putative recognition sites for PtdIns(3,4,5)P,.
|Publication status||Published - 1997 Dec 1|
All Science Journal Classification (ASJC) codes
- Molecular Biology