CIRCULAR-DICHROISM STUDIES OF THE INTERACTION BETWEEN SYNTHETIC PEPTIDES CORRESPONDING TO INTRACELLULAR LOOPS OF BETA-ADRENERGIC RECEPTORS AND PHOSPHOLIPID-VESICLES

We previously showed that peptides corresponding to the N-terminal par ts of the third intracellular loops of turkey and hamster beta-adrener gic receptors (tu beta I3N and ha beta I3N, respectively) can activate the G(s) protein (one of the GTP-binding regulatory proteins which co uples to the beta-adrenergic receptor) reconstituted in phospholipid v esicles, and also that such activation can be greatly enhanced by a mo dification which increases the hydrophobicity of the peptides. These o bserved phenomena suggest that the interaction with phospholipid membr anes is important for the activity of these peptides; hence, in the pr esent study we employed circular dichroism to analyze the interaction of the synthetic peptides corresponding to the intracellular loops of G protein-coupled receptors with phosphatidylserine/phosphatidylcholin e mixed vesicles. The tu beta I3N and ha beta I3N peptides were subseq uently found to take on an alpha-helical conformation upon binding wit h the vesicles, whereas those corresponding to the intracellular loops of m1 and m2 muscarinic acetylcholine receptors in contrast did not i nteract with the vesicles. The positions of several side chains of the membrane-bound loop peptides were also determined. Our results show f or the first time the interaction occurring between the intracellular loops of beta-adrenergic receptors and a phospholipid membrane.