Function of the delipidated beta-adrenergic receptor appears to require a fatty acid or a neutral lipid in addition to phospholipids.
Detergent-solubilized preparations of the beta-adrenergic receptor (R) and of the guanyl nucleotide binding proteins (Gs) were extensively treated to remove phospholipids and cholesterol. Reconstitution of an R-Gs system was subsequently performed in the presence of a mixture of natural phosphatidylethanolamine, phosphatidylcholine and phosphatidylserine or the synthetic dioleoyl derivatives of the same phospholipids. In both cases, an additional lipid was required for the agonist-dependent activation of Gs. The requirement could be fulfilled by alpha-tocopherol, or by unsaturated fatty acids such as oleic acid. Inclusion of this non-phosphorylated lipid in the reconstituted system enhanced the isoproterenol-dependent activation of Gs by guanosine 5'-O-[gamma-thio]triphosphate 16-33-fold. The rate of activation was largely dependent on the addition of the agonist. Efficient functional reconstitution of R-Gs was thus achieved in a totally defined lipid system. Additional studies of the reconstituted system and of the native membrane led to the notion that the non-phosphorylated lipid plays a role in the function of the hormone-R complex.
D000818:Animals; D004910:Erythrocyte Membrane / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D009829:Oleic Acids / Q000502:physiology; D010743:Phospholipids / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012995:Solubility; D014422:Turkeys; D014810:Vitamin E / Q000502:physiology*
D005231:Fatty Acids, Unsaturated; D009829:Oleic Acids; D010743:Phospholipids; D011943:Receptors, Adrenergic, beta; D014810:Vitamin E; D019204:GTP-Binding Proteins; D007545:Isoproterenol