Tertiary and quaternary structural changes in Giα1 induced by GTP hydrolysis

Mark B. Mixon, Ethan Lee, David E. Coleman, Albert M. Berghuis, Alfred G. Gilman, Stephen R. Sprang

Research output: Contribution to journalArticlepeer-review

275 Scopus citations


Crystallographic analysis of 2.2 angstrom resolution shows that guanosine triphosphate (GTP) hydrolysis triggers conformational changes in the heterotrimeric G-protein α subunit, Giα1. 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 βγ 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 βγ 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 a subunits or heterotrimers may play a role in signal transduction.

Original languageEnglish
Pages (from-to)954-960
Number of pages7
Issue number5238
StatePublished - 1995


Dive into the research topics of 'Tertiary and quaternary structural changes in Giα1 induced by GTP hydrolysis'. Together they form a unique fingerprint.

Cite this