Tertiary and Quaternary Structural Changes in G iα1 Induced by GTP Hydrolysis

Abstract

Crystallographic analysis of 2.2 angstrom resolution shows that guanosine triphosphate (GTP) hydrolysis triggers conformational changes in the heterotrimeric G-protein α subunit, G iα1 . The switch II and switch III segments become disordered, and linker II connecting the Ras and α helical domains moves, thus altering the structures of potential effector and β γ binding regions. Contacts between the α-helical and Ras domains are weakened, possibly facilitating the release of guanosine diphosphate (GDP). The amino and carboxyl termini, which contain receptor and β γ binding determinants, are disordered in the complex with GTP, but are organized into a compact microdomain on GDP hydrolysis. The amino terminus also forms extensive quaternary contacts with neighboring α subunits in the lattice, suggesting that multimers of α subunits or heterotrimers may play a role in signal transduction.