Interaction of a G protein with an activated receptor opens the interdomain interface in the alpha subunit.

ABSTRACT: In G-protein signaling, an activated receptor catalyzes GDP/GTP exchange on the G(?) subunit of a heterotrimeric G protein. In an initial step, receptor interaction with G(?) acts to allosterically trigger GDP release from a binding site located between the nucleotide binding domain and a helical domain, but the molecular mechanism is unknown. In this study, site-directed spin labeling and double electron-electron resonance spectroscopy are employed to reveal a large-scale separation of the domains that provides a direct pathway for nucleotide escape. Cross-linking studies show that the domain separation is required for receptor enhancement of nucleotide exchange rates. The interdomain opening is coupled to receptor binding via the C-terminal helix of G(?), the extension of which is a high-affinity receptor binding element.

SUBMITTER: Van Eps N 

PROVIDER: S-EPMC3111277 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature