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NMR structure of a receptor-bound G-protein peptide

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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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Author notes

  1. Christophe G. Lambert

    Present address: Department of Computer Science, Duke University, Durham, North Carolina, 27708, USA

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana, 59717, USA

    Edward A. Dratz, Julie E. Furstenau, Christophe G. Lambert & Dennis L. Thireault

  2. Department of Physiology and Biophysics, University of Illinois College of Medicine at Chicago, Chicago, Illinois, 60680, USA

    Helen Rarick, Theresa Schepers, Sergei Pakhlevaniants & Heidi E. Hamm

  3. Department of Ophthalmology, University of Illinois College of Medicine at Chicago, Chicago, Illinois, 60680, USA

    Heidi E. Hamm

  4. Istituto di Fisiologia Generale e Chimica Biologica, Universita' di Sassari, 07100, Sassari, Italy

    Heidi E. Hamm

Authors
  1. Edward A. Dratz
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  2. Julie E. Furstenau
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  4. Dennis L. Thireault
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  5. Helen Rarick
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  7. Sergei Pakhlevaniants
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  8. Heidi E. Hamm
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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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