Two sites in the third inner loop of the dopamine D2 receptor are involved in functional G protein-mediated coupling to adenylate cyclase.
Synthetic peptides, corresponding to the amino acid sequences of the N- and C-terminal parts of the 3rd intracellular loop of the dopamine D2 receptor, attenuate dopaminergic adenylate cyclase inhibition in membranes. Both peptides also activate directly GTPase activity in membranes. We suggest a functional model for G(i)-coupled receptors where two sites in the 3rd inner loop compose the links for the receptor-G protein interaction thus providing the tools for a selective and adjustable response. Functional coupling was not affected by a peptide representing the insert in the long form of the dopamine D2 receptor (D2(long)). The selectivity pattern of conventional G protein-linked receptors also sheds some light on the recently observed interaction of beta-amyloid protein precursor (APP) complexes with G proteins.
Malek
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Theodor-Boveri-Institut für Biowissenschaften, Physiologische Chemie I, Universität Würzburg, Germany.
Münch
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Palm
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D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D017448:Receptors, Dopamine D2; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases