Figure 4 - full size


Figure 4.
Fig. 4. Emerging themes for protein-protein interactions mediated by G [q] and PH domains and a model for p63RhoGEF activation by G [i/q]. (A) The p63RhoGEF PH domain in complex with G [i/q]. Inositol 1,4,5-trisphosphate (IP[3]) is modeled based on the phospholipase C– PH domain·IP[3] complex (29) to help define the expected plane of the lipid bilayer. (B) GRK2 binds similarly to the G [i/q]effector-binding site, using exposed hydrophobic residues in its 5 helix. Only the 5 and 6 helices of the GRK2 RH domain are shown. In both the p63RhoGEF and GRK2 complexes, G [i/q] is held in an orientation in which its longest axis is roughly parallel and switch I is held relatively close to the predicted membrane surface (top). In both complexes, the switch I region appears available for the simultaneous binding of regulator of G protein signaling proteins (30). (C) The GRK2 and p63RhoGEF PH domains engage their protein targets in a similar way, using a C-terminal helical extension and the loops at one edge of the β1-β4 sheet of the PH domain to form an extensive protein interaction site (Fig. 3). (D) The DH and PH domains of p63RhoGEF adopt a conformation distinct from that of Dbs (black). The view is the same as in Fig. 2A. The bridging interactions of G [i/q] (spheres) appear to rotate the position of the p63RhoGEF PH domain away from the RhoA binding site on the DH domain, along the plane of the membrane surface.

The above figure is reprinted by permission from the AAAs: Science (2007, 318, 1923-1927) copyright 2007.