Structural properties of the alpha 1-adrenergic receptor: studies with membrane and purified receptor preparations.
The contribution of hydrophobic, ionic, and disulfide bonds in the alpha 1-adrenergic receptor structure was evaluated using rat hepatic plasma membrane and purified receptor preparations. In addition, the findings were compared with similar structural evaluations of the beta 2-adrenergic receptor purified from canine lung. Both the alpha 1- and beta 2-adrenergic receptors contain a disulfide bond critical for ligand binding. However, the disulfide bond in the beta-receptor structure is accessible to solvent, while the disulfide bond within the alpha-receptor structure is "masked" and inaccessible to solvent. Reduction of this disulfide bond requires initial denaturation of the alpha 1-receptor. Although the tertiary structures of both receptor proteins appear to be stabilized by strong hydrophobic interactions, differential sensitivities are observed with a variety of structural perturbants, including high concentrations of sodium chloride, guanidine hydrochloride, and ethylene glycol.
Parini
A
A
Cellular and Molecular Research Laboratory, Massachusetts General Hospital, Boston 02114.
Homcy
C J
CJ
Graham
R M
RM
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004220:Disulfides / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D019855:Ethylene Glycol; D005026:Ethylene Glycols / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology
D004220:Disulfides; D005026:Ethylene Glycols; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D012965:Sodium Chloride; D019855:Ethylene Glycol; D004229:Dithiothreitol