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G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay
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G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay

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G-protein diseases furnish a model for the turn-on switch

T Iiri1, Z Farfel, H R Bourne

  • 1Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143-0450, USA.

Nature
|July 17, 1998
PubMed

Insights

Trimeric G proteins inside cell membranes activate via transmembrane receptors. Mutations in these proteins cause diseases like hypertension, revealing how signals are relayed.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Trimeric G proteins are crucial intracellular signal transducers.
  • Their activation by transmembrane receptors initiates diverse cellular responses.
  • Dysregulation of G protein signaling is linked to human diseases.

Purpose of the Study:

  • To elucidate the molecular mechanism of trimeric G protein activation by transmembrane receptors.
  • To understand how G-protein mutations contribute to diseases like hypertension and endocrine disorders.

Main Methods:

  • Analysis of G-protein mutations in patients.
  • Utilizing three-dimensional crystal structures.
  • Conducting biochemical experiments.

Main Results:

  • G-protein mutations were found to either enhance or block signals from stimulated receptors.
  • These findings, combined with structural and biochemical data, suggest a model for activation.
  • The model explains signal relay from hormonal and sensory inputs.

Conclusions:

  • A model for trimeric G protein activation by transmembrane receptors has been proposed.
  • This model integrates structural, biochemical, and clinical data.
  • Understanding this mechanism is key to deciphering hormonal and sensory signal transduction.

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