THE STRUCTURE OF THE G-PROTEIN HETEROTRIMER G(I-ALPHA-1)BETA(1)GAMMA(2)

The crystallographic structure of the G protein heterotrimer G(i alpha 1)(GDP)beta 1(1 gamma 2) (at 2.3 Angstrom) reveals two nonoverlapping regions of contact between alpha and beta, an extended interface between beta and nearly all of gamma, and limited interaction of alpha with gamma. The major alpha/beta interface covers switch II of alpha, and GTP-induced rearrangement of switch II causes subunit dissociation during signaling. Alterations in GDP binding in the heterotrimer (compared with alpha-GDP) explain stabilization of the inactive conformation of alpha by beta gamma. Repeated WD motifs in beta form a circularized sevenfold beta propeller. The conserved cores of these motifs are a scaffold for display of their more variable linkers on the exterior face of each propeller blade.