Microscopic Characterization of GRP1 PH Domain Interaction with Anionic Membranes.

ABSTRACT: The pleckstrin homology (PH) domain of general receptor for phosphoionositides 1 (GRP1-PHD) binds specifically to phosphatidylinositol (3,4,5)-triphosphate (PIP₃ ), and acts as a second messenger. Using an extensive array of molecular dynamics (MD) simulations employing highly mobile membrane mimetic (HMMM) model as well as complementary full membrane simulations, we capture differentiable binding and dynamics of GRP1-PHD in the presence of membranes containing PC, PS, and PIP₃ lipids in varying compositions. While GRP1-PHD forms only transient interactions with pure PC membranes, incorporation of anionic lipids resulted in stable membrane-bound configurations. We report the first observation of two distinct PIP₃ binding modes on GRP1-PHD, involving PIP

SUBMITTER: Pant S 

PROVIDER: S-EPMC7000246 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature