Showing papers by "Richard M. Epand published in 1983"
TL;DR: The ability of human calcitonin to solubilize dimyristoylphosphatidylglycerol and to alter the phase transition properties of this phospholipid while maintaining a low content of helix indicates that the presence of an amphipathic helix is not a requirement for these effects.
Abstract: Salmon, porcine, and human calcitonins interact with phosphatidylglycerol to form water-soluble complexes, but these peptides do not interact with the zwitterionic lipids phosphatidylcholine or sphingomyelin. The calcitonins are more helical in the presence of dimyristoylphosphatidylglycerol than in its absence, but human calcitonin is considerably less helical than the other two, particularly in the presence of the lipid. This may explain the previously reported faster rate of degradation of human compared with salmon calcitonin in vivo. The ability of human calcitonin to solubilize dimyristoylphosphatidylglycerol and to alter the phase transition properties of this phospholipid while maintaining a low content of helix indicates that the presence of an amphipathic helix is not a requirement for these effects. The binding of salmon calcitonin to dimyristoylphosphatidylglycerol has been studied by determining the dependence of the circular dichroism properties of the peptide on the concentration of lipid. At 25 degrees C, salmon calcitonin binds to five molecules of dimyristoylphosphatidylglycerol with an affinity constant of 1 X 10(5) M-1. Little change in these parameters is observed at 38 degrees C, and the complex is stable over a wide range of temperatures both above and below the phase transition temperature. The rate of reaction of salmon calcitonin with dimyristoylphosphatidylglycerol is rapid at or above the phase transition temperature of the lipid but not at low temperatures. Salmon calcitonin also interacts with egg phosphatidylglycerol. These results demonstrate that salmon calcitonin can react with phosphatidylglycerol at or above its phase transition temperature to form complexes which are at least kinetically stable both above and below the phase transition temperature. Salmon calcitonin can solubilize mixtures of dimyristoylphosphatidylglycerol and dimyristoylphosphatidylcholine containing 25% or more of the former phospholipid. The helical content of the peptide in the presence of these lipid mixtures is dependent on the fraction of the lipid which is phosphatidylglycerol, with larger fractions of this lipid leading to the formation of a higher helical content. At 25% phosphatidylglycerol, salmon calcitonin can solubilize the lipid mixture without much increase in the helix content of the peptide, again demonstrating that an amphipathic helical structure is not required for the solubilization of phospholipids. Ionic bonding appears to be an important component in the binding of the cationic calcitonins to phospholipids. Salmon calcitonin binds to the acidic phospholipids phosphatidylinositol and phosphatidic acid, but not to zwitterionic phospholipids. In addition, high concentrations of NaCl cause the dissociation of the complex between salmon calcitonin and dimyristoylphosphatidylglycerol.(ABSTRACT TRUNCATED AT 400 WORDS)
119 citations
TL;DR: The phase transition behavior of dilauroylphosphatidylethanolamine dispersion at physiological pH and temperature and in the presence of excess water was studied in this paper.
97 citations
TL;DR: A model is proposed in which all regions of the hormone bind to the receptor with comparable affinity except for a small segment which, when intact, triggers a conformational change in the receptor resulting in a further stabilization of the hormones-receptor complex.
Abstract: Several polypeptide hormones of apparently diverse structure and function have a number of similarities which suggest that there may be common features in their mechanism of action. These hormones are all composed of a single linear sequence of about 30 amino acids; their hydrophobic amino acids are regularly spaced at every third or fourth amino acid residue, allowing them to form amphipathic structures which can interact with phospholipids; a fragment at or near their N-terminus is required for biological activity. These hormones include glucagon, beta-endorphin, parathyroid hormone and calcitonin. A model is proposed in which all regions of the hormone bind to the receptor with comparable affinity except for a small segment which, when intact, triggers a conformational change in the receptor resulting in a further stabilization of the hormone-receptor complex. The activity of partial sequences and chemically modified forms of beta-endorphin, parathyroid hormone and glucagon are discussed in relation to this model.
35 citations
TL;DR: Structural-function studies of glucagon suggest that relatively non-specific hydrophobic interactions participate in the binding of this hormone to cell surface receptors and may occur as a result of the formation of segments of amphipatic helix in the peptide.
25 citations
TL;DR: The interaction between glucagon and dicaprylphosphatidylcholine was studied by fluorescence, circular dichroism and calorimetry, as well as by 1 H- and 31 P-nuclear magnetic resonance, demonstrating that the complex formed between glucagons and DCPC is stable over a wide range of temperatures, including temperatures well above the phase transition.
2 citations
01 Jul 1983
TL;DR: Two- to five-fold higher concentrations of glucagon are required for half-maximal stimulation of adenylate cyclase when the hormone is complexed with dimyristoyl phosphatidylcholine, dipalmitoyl phosphate, or bovine brain sphingomyelin, and a possible role of lipoprotein-associated hormones in the development of insulin resistance is discussed.
Abstract: Glucagon can form water-soluble complexes with phospholipids. The incorporation of glucagon into these lipoprotein particles reduces the biological activity of the hormone. The effect is observed only at temperatures below the phase transition temperature of the phospholipid and results in a decreased stimulation of the adenylate cyclase of rat liver plasma membranes by the lipoprotein complex as compared with the hormone in free solution. Two- to five-fold higher concentrations of glucagon are required for half-maximal stimulation of adenylate cyclase when the hormone is complexed with dimyristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, or bovine brain sphingomyelin. A possible role of lipoprotein-associated hormones in the development of insulin resistance is discussed.
2 citations
TL;DR: The trinitrophenyl group was specifically introduced into the epsilon-amino group of glucagon by reaction of N alpha-citraconyl glucagon with trinitrobenzenesulfonic acid, which was subsequently removed by acid treatment yielding N ePSilon-trinitropenyl glucagon which was purified by anion-exchange chromatography.