Dimers of G-protein coupled receptors as versatile storage and response units

Int J Mol Sci. 2014 Mar 19;15(3):4856-77. doi: 10.3390/ijms15034856.

Abstract

The status and use of transmembrane, extracellular and intracellular domains in oligomerization of heptahelical G-protein coupled receptors (GPCRs) are reviewed and for transmembrane assemblies also supplemented by new experimental evidence. The transmembrane-linked GPCR oligomers typically have as the minimal unit an asymmetric ~180 kDa pentamer consisting of receptor homodimer or heterodimer and a G-protein αβγ subunit heterotrimer. With neuropeptide Y (NPY) receptors, this assembly is converted to ~90 kDa receptor monomer-Gα complex by receptor and Gα agonists, and dimers/heteropentamers are depleted by neutralization of Gαi subunits by pertussis toxin. Employing gradient centrifugation, quantification and other characterization of GPCR dimers at the level of physically isolated and identified heteropentamers is feasible with labeled agonists that do not dissociate upon solubilization. This is demonstrated with three neuropeptide Y (NPY) receptors and could apply to many receptors that use large peptidic agonists.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Arrestin / chemistry
  • Arrestin / metabolism
  • Binding Sites
  • Binding, Competitive / drug effects
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Humans
  • Kinetics
  • Neuropeptide Y / metabolism
  • Neuropeptide Y / pharmacology
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Peptide YY / metabolism
  • Peptide YY / pharmacology
  • Protein Binding / drug effects
  • Protein Multimerization*
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Rabbits
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Neuropeptide Y / agonists
  • Receptors, Neuropeptide Y / chemistry*
  • Receptors, Neuropeptide Y / metabolism

Substances

  • Arrestin
  • Neuropeptide Y
  • Peptide Fragments
  • Protein Subunits
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide Y
  • Peptide YY
  • peptide YY (3-36)