title: 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(α) subunit of a heterotrimeric G protein. In an initial step, receptor interaction with G(α) 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(α), the extension of which is a high-affinity receptor binding element.
authors: Jules Stein Eye Institute and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-7008, USA.
authors: Ned
authors: N
authors: Van Eps
authors: Anita M
authors: AM
authors: Preininger
authors: Nathan
authors: N
authors: Alexander
authors: Ali I
authors: AI
authors: Kaya
authors: Scott
authors: S
authors: Meier
authors: Jens
authors: J
authors: Meiler
authors: Heidi E
authors: HE
authors: Hamm
authors: Wayne L
authors: WL
authors: Hubbell
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