Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Under reducing conditions of SDS-polyacrylamide gel electrophoresis, the CB(1) receptor exists in its monomeric form as well as in an SDS-resistant high molecular weight form that appears to be devoid of G proteins. The CB(1) cannabinoid receptor was immunoprecipitated from 3-[(3-cholamidopropyl)dimethylammonio]propanesulfonate-solubilized rat brain membranes using an antibody against the CB(1) receptor N terminus. The CB(1) receptor was coimmunoprecipitated with its associated G proteins, specifically those of the Galpha(i/o) family, but not Galpha(s), Galpha(q), or Galpha(z). The CB(1) receptor-Galpha(i/o) complex existed in the absence of exogenous agonists, and the cannabinoid receptor agonist desacetyllevonantradol failed to alter the stoichiometry of the receptor-Galpha(i/o) interaction. Guanosine-5'-O-(3-thio)triphosphate could disrupt the interaction. A peptide derived from the CB(1) receptor juxtamembrane C-terminal domain, peptide CB(1)401-417, autonomously activates G(i/o) proteins. Peptide CB(1)401-417 competitively disrupted the CB(1) receptor association with Galpha(o) and Galpha(i3) but not Galpha(i1) or Galpha(i2). This G protein specificity was also observed in detergent extracts from membranes of the frontal cortex, striatum, and cerebellum. Alternative peptides, including peptides from the CB(1) receptor third intracellular loop and the G protein activating peptide mastoparan-7, failed to promote uncoupling from Galpha(o). A CB(2) receptor juxtamembrane C-terminal peptide failed to disrupt the CB(1) receptor-Galpha(o) complex. These studies illustrate that the CB(1) receptor can exist as an SDS-resistant multimer. In 3-[(3-cholamidopropyl)dimethylammonio]propanesulfonate detergent, the CB(1) receptor exists in a complex with G proteins of the G(i/o) family in the absence of exogenous agonists. Furthermore, this study provides the first description of domain specificity for interaction with a selective set of G proteins.
 ...
PMID:The CB(1) cannabinoid receptor juxtamembrane C-terminal peptide confers activation to specific G proteins in brain. 1061 91

The proximal portion of the C-terminus of the CB(1) cannabinoid receptor is a primary determinant for G-protein activation. A 17 residue proximal C-terminal peptide (rodent CB1 401-417), the intracellular loop 4 (IL4) peptide, mimicked the receptor's G-protein activation domain. Because of the importance of the cationic amino acids to G-protein activation, the three-dimensional structure of the IL4 peptide in a negatively charged sodium dodecyl sulfate (SDS) micellar environment has been studied by two-dimensional proton nuclear magnetic resonance (2D (1)H NMR) spectroscopy and distance geometry calculations. Unambiguous proton NMR assignments were carried out with the aid of correlation spectroscopy (DQF-COSY and TOCSY) and nuclear Overhauser effect spectroscopy (NOESY and ROESY) experiments. The distance constraints were used in torsion angle dynamics algorithm for NMR applications (DYANA) to generate a family of structures which were refined using restrained energy minimization and dynamics. In water, the IL4 peptide prefers an extended conformation, whereas in SDS micelles, 3(10)-helical conformation is induced. The predominance of 3(10)-helical domain structure in SDS represents a unique difference compared with structure in alternative environments, which can significantly impact global electrostatic surface potential on the cytoplasmic surface of the CB(1) receptor and might influence the signal to the G-proteins.
 ...
PMID:Unique helical conformation of the fourth cytoplasmic loop of the CB1 cannabinoid receptor in a negatively charged environment. 1752 64