TERTIARY AND QUATERNARY STRUCTURAL-CHANGES IN G(I-ALPHA-1) INDUCED BYGTP HYDROLYSIS

Crystallographic analysis of 2.2 angstrom resolution shows that guanos ine triphosphate (GTP) hydrolysis triggers conformational changes in t he heterotrimeric G-protein alpha subunit, G(i alpha 1). The switch II and switch III segments become disordered, and linker II connecting t he Ras and alpha helical domains moves, thus altering the structures o f potential effector and beta gamma binding regions. Contacts between the alpha-helical and Ras domains are weakened, possibly facilitating the release of guanosine diphosphate (GDP). The amino and carboxyl ter mini, which contain receptor and beta gamma binding determinants, are disordered in the complex with GTP, but are organized into a compact m icrodomain on GDP hydrolysis. The amino terminus also forms extensive quaternary contacts with neighboring alpha subunits in the lattice, su ggesting that multimers of alpha subunits or heterotrimers may play a role in signal transduction.