Allosteric properties of PH domains in Arf regulatory proteins.
Pleckstrin Homology (PH) domains bind phospholipids and proteins. They are critical regulatory elements of a number enzymes including guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) for Ras-superfamily guanine nucleotide binding proteins such as ADP-ribosylation factors (Arfs). Recent studies have indicated that many PH domains may bind more than one ligand cooperatively. Here we discuss the molecular basis of PH domain-dependent allosteric behavior of 2 ADP-ribosylation factor exchange factors, Grp1 and Brag2, cooperative binding of ligands to the PH domains of Grp1 and the Arf GTPase-activating protein, ASAP1, and the consequences for activity of the associated catalytic domains.
Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health , Bethesda, MD, USA.
Neeladri Sekhar
NS
Roy
Genetics Branch, National Cancer Institute, National Institutes of Health , Bethesda, MD, USA.
Marielle E
ME
Yohe
Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health , Bethesda, MD, USA.
Paul A
PA
Randazzo
Laboratory of Structural Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health , Bethesda, MD, USA.
James M
JM
Gruschus
ADP-ribosylation factor; GTPase-activating protein; Pleckstrin homology; allosterism; cooperativity; guanine nucleotide exchange factor