Finding a needle in a haystack: the role of electrostatics in target lipid recognition by PH domains.

ABSTRACT: Interactions between protein domains and lipid molecules play key roles in controlling cell membrane signalling and trafficking. The pleckstrin homology (PH) domain is one of the most widespread, binding specifically to phosphatidylinositol phosphates (PIPs) in cell membranes. PH domains must locate specific PIPs in the presence of a background of approximately 20% anionic lipids within the cytoplasmic leaflet of the plasma membrane. We investigate the mechanism of such recognition via a multiscale procedure combining Brownian dynamics (BD) and molecular dynamics (MD) simulations of the GRP1 PH domain interacting with phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P₃). The interaction of GRP1-PH with PI(3,4,5)P₃ in a zwitterionic bilayer is compared with the interaction in bilayers c

SUBMITTER: Lumb CN 

PROVIDER: S-EPMC3406000 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature