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

Van Eps N, Preininger AM, Alexander N, Kaya AI, Meier S, Meiler J, Hamm HE, Hubbell WL
Proc Natl Acad Sci U S A. 2011 108 (23): 9420-4

PMID: 21606326 · PMCID: PMC3111277 · DOI:10.1073/pnas.1105810108

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.

MeSH Terms (19)

Amino Acid Sequence Animals Cell Membrane Cross-Linking Reagents Electron Spin Resonance Spectroscopy GTP-Binding Protein alpha Subunits GTP-Binding Proteins Guanosine Diphosphate Guanosine Triphosphate Models, Molecular Molecular Sequence Data Mutation Protein Binding Protein Structure, Secondary Protein Structure, Tertiary Rats Receptors, G-Protein-Coupled Rhodopsin Spin Labels

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