A Selective Survey of Ga Protein Structure and Function

The G12 family proteins Gal2 and Gal3 are regulators of a family of RhoGEFs (Hart et at, 1998). Effectors within this family exhibit GAP activity toward Gal2/13 (Kozasa et at, 1998) recent biochemical and structural studies, described here and in the chapter by Sternweis et at in this volume, have begun to suggest how GAP and effector-stimulatory activity are coupled in this family of effectors. 

The physical basis of the kinetic linkage between GTP hydrolysis and conformational change arises from the involvement of Switch I and Switch II in both processes. The P-loop, or Walker A motif (Walker et at, 1982) 

Two of the Gy effector complexes that we describe in this chapter involve interactions between the Ga protein and RGS-like domains of the effector. As discussed in greater detail in Section V, many RGS domains exhibit GAP activity toward Ga. This is true for the major family of RGS domains whose members share substantial sequence similarity. The RGS-like domains of pll5RhoGEF and GRK2 belong to separate and distinct subgroups that bear only remote sequence similarity to the larger family of RGS GAPs, and bind to Ga in the mode characteristic of effectors. 

The Ga effector-recognition knob is formed by residues near the a3-/15 junction. In all Ga isoforms except for Gal 3 and Gal 2, a tryptophan residue (Trp 234 in Gas) constitutes the knob that fits into a complementary cavity in the effector. Mutation of the a3 tryptophan and surrounding 

Although Ga proteins exhibit considerable selectivity, effector-binding surfaces can nevertheless tolerate substantial variation. That is why it has been possible to use chimeric Ga proteins in structural studies of G protein effector complexes. Some Ga isoforms are difficult to express in heterologous 

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