Comparative analysis of the regions binding beta gamma-subunits in Galpha and PH domains.

Some of the pleckstrin homology (PH) domains are shown to bind beta gamma-subunits of a G-protein. In this paper we present a detailed comparison of sequences and structural features of beta gamma-binding regions in PH domains and alpha-subunits (G alpha) of known structure. Our comparison involves switch II region in G alpha and a C-terminal region of PH domain structures and we suggest a similarity in these regions. By comparing the active and inactive forms of G alpha structures we predict that some of the bulky hydrophobic residues in switch II region might interact with beta gamma-subunits. Subsequent to completion of this work we find that this prediction is absolutely consistent with recently reported crystal structures of heterotrimeric G-proteins. We discuss the feasibility of common principles in the recognition G alpha and PH domains by beta gamma-subunits.