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Effects of phosphoinositide identity and lateral organization on PTEN binding and structure
Author(s) -
Gericke Arne,
Redfern Roberta E,
Ross Alonzo H
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a978-a
Subject(s) - pten , vesicle , phosphatidylinositol , inositol , phosphatase , chemistry , conformational change , pi , biophysics , quenching (fluorescence) , membrane , fluorescence , biochemistry , receptor , signal transduction , biology , pi3k/akt/mtor pathway , phosphorylation , physics , quantum mechanics
PTEN is a phosphatidylinositol phosphate (PIP) phosphatase specific for the 3‐position of the inositol ring. Recent reports have shown that PTEN is activated by PI(4,5)P 2 and that this activation requires a polybasic region located at the N‐terminus of the protein. It was hypothesized that PI(4,5)P 2 aids membrane recruiting and induces a conformational change in PTEN. This study characterizes PTENs binding preferences, investigates its contact points with the lipid bilayer and highlights structural changes upon membrane interaction. Fluorescence quenching experiments involving PC/phosphoinositide vesicles yielded results consistent with an enhanced PTEN binding to PI(4,5)P 2 or PI(5)P containing vesicles, while the interaction with all other phosphoinositide derivatives was only minor. Experiments with a truncated PTEN 16‐403 showed a strongly reduced phosphoinositide affinity and a loss of specificity, while experiments using a peptide representing PTENs N‐terminus (PTEN 1‐21 ) showed preferential PI(4,5)P 2 binding. Infrared spectroscopic measurements furnished results consistent with an increased α‐helical secondary structure content in the presence of PI(4,5)P 2 /PC vesicles, while other phosphoinositides like PI(3,5)P 2 or PI(3,4,5)P 3 did not cause a structural change. Although PS induced a structural change towards more β‐sheet, it did not alter the structural effect of PI(4,5)P 2 .