Surface properties of an amphiphilic peptide hormone and of its analog: corticotropin-releasing factor and sauvagine.
Synthetic corticotropin (adrenocorticotropic hormone)-releasing factor [CRF; for the sequence, see Vale, W., Spiess, J., Rivier, C. & Rivier, J. (1981) Science 213, 1394-1397] in aqueous solution exists predominantly as a random coil. At concentrations greater than 1 microM, the peptide shows a tendency to self-aggregate with a concurrent slight increase in the apparent alpha-helical content as measured by the CD spectrum. The alpha-helix formed by this molecule is highly amphiphilic--i.e., the hydrophilic and hydrophobic regions are segregated on opposite faces of the helix. As predicted from the potential amphiphilic structure, CRF binds avidly to the surface of single bilayer egg phosphatidylcholine vesicles. This binding appears to obey a simple Langmuir isotherm with the following parameters: Kd = 1.3 +/- 0.6 X 10(-7) M and capacity at saturation (N) = 11.0 +/- 1.0 mmol of peptide per mol of phospholipid. CRF also readily forms an insoluble monolayer at the air-water interface. The monolayer is composed of monomers of the hormone with molecular areas, A'0 = 22 A2 per amino acid, suggesting a compact secondary structure. Judged from the collapse pressure (19.0 +/- 0.1 dyne/cm; 1 dyne = 10 microN) of the monolayer, the amphiphilicity of CRF approximates that of plasma apolipoproteins, a class of proteins of the most pronounced amphiphilic character. These results suggest that the binding of CRF to the cell membrane is accompanied by the induction of an alpha-helical secondary structure and it is this predominantly helical form that is the biologically active form of the peptide.
D000595:Amino Acid Sequence; D029845:Amphibian Proteins; D002942:Circular Dichroism; D003346:Corticotropin-Releasing Hormone; D007700:Kinetics; D008081:Liposomes; D036361:Peptide Hormones; D010455:Peptides; D010713:Phosphatidylcholines; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014665:Vasodilator Agents
D029845:Amphibian Proteins; D008081:Liposomes; D036361:Peptide Hormones; D010455:Peptides; D010713:Phosphatidylcholines; D014665:Vasodilator Agents; C025727:sauvagine; D003346:Corticotropin-Releasing Hormone