Membrane association of the PTEN tumor suppressor: molecular details of the protein-membrane complex from SPR binding studies and neutron reflection.

ABSTRACT: The structure and function of the PTEN phosphatase is investigated by studying its membrane affinity and localization on in-plane fluid, thermally disordered synthetic membrane models. The membrane association of the protein depends strongly on membrane composition, where phosphatidylserine (PS) and phosphatidylinositol diphosphate (PI(4,5)P(2)) act pronouncedly synergistic in pulling the enzyme to the membrane surface. The equilibrium dissociation constants for the binding of wild type (wt) PTEN to PS and PI(4,5)P(2) were determined to be K(d)∼12 µM and 0.4 µM, respectively, and K(d)∼50 nM if both lipids are present. Membrane affinities depend critically on membrane fluidity, which suggests multiple binding sites on the protein for PI(4,5)P(2). The PTEN mutations C124S and H93R show bindi

SUBMITTER: Shenoy S 

PROVIDER: S-EPMC3323581 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature