Abstract
HETEROTRIMERIC GTP-binding proteins (G proteins) regulate cellular activity by coupling to hormone or sensory receptors. Stimulated receptors catalyse the release of GDP from G protein α-subunits1–4 and GTP bound to the empty α-subunits provides signals that control effectors such as adenylyl cyclases, phos-phodiesterases, phospholipases and ion channels4. Three cytoplas-mic loops of the activated receptor are thought to interact with three sites on the heterotrimeric G protein to provide high-affinity interaction and catalyse G-protein activation5–8. The carboxyl terminus of the α-subunit is particularly important for interaction with the receptor9–14. Here we study the structure of part of the active interface between the photon receptor rhodopsin and the G protein transducin, or Gt, using nuclear magnetic resonance. An 11-amino-acid peptide from the C terminus of the α-summit of Gt (αt (340–350)) binds to rhodopsin and mimics the G protein in stabilizing its active form, metarhodopsin II. The peptide αt(340–350) binds to both excited and unexcited rhodopsin and conformational differences between the two bound forms suggest a mechanism for activation of G proteins by agonist-stimulated receptors. Insight into receptor-catalysed GDP release will have broad application because the GTP/GDP exchange and the intrinsic GTPase activity of GTP-binding proteins constitute a widespread regulatory mechanism15.
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Dratz, E., Furstenau, J., Lambert, C. et al. NMR structure of a receptor-bound G-protein peptide. Nature 363, 276–281 (1993). https://doi.org/10.1038/363276a0
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DOI: https://doi.org/10.1038/363276a0
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