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51.
The interaction between glucagon and dicaprylphosphatidylcholine (DCPC) was studied by fluorescence, circular dichroism and calorimetry, as well as by 1H- and 31P-nuclear magnetic resonance. The water-soluble lipid-protein complex was also characterized by gel filtration and ultracentrifugation. The complex appeared to be monodisperse by sedimentation equilibrium measurements, with a molecular weight of (4.55 ± 0.57)·104. This complex contained approximately 7 molecules of glucagon and 35 molecules of phospholipid. Proton-decoupled 31P-NMR spectra of the phospholipid in the lipid-protein complex display narrower resonances than those of sonicated vesicles of DCPC, and 1H-31P coupling could be detected in proton coupled spectra. These NMR results, together with gel-filtration results, suggest that glucagon ‘solubilizes’ phospholipid aggregates, forming a lipid-protein complex which is smaller than sonicated preparations of DCPC. 1H-NMR resonance of both the methionine methyl group (met-27) and the aromatic envelope of glucagon are broadened by the phospolipid, indicating that the C-terminal region and the aromatic residues are involved in the interaction with the phospholipid. Nuclear magnetic resonance titrations of the imidazole ring C(2) and C(4) protons of the histidine residue of glucagon show that DCPC lowers the pK of the imidazole. The alterations caused by the phospholipid in the far and near ultraviolet CD spectra of glucagon reflect, respectively, the increased helix content of the hormone and the fact that the aromatic residues are located in a more structured environment. The phospholipid also alters the fluorescence properties of glucagon, shifting the fluorescence emission maximum of the hormone to shorter wavelength, and enhancing its relative intensity. This suggests that the fluorophore is experiencing a more hydrophobic environment in the presence of the lipid. Binding of glucagon to the phospholipid was analysed by Scatchard plots of the enhancement of fluorescence caused by the phospholipid and showed that the equilibrium binding constants of glucagon to DCPC are (4.4 ± 0.5)·104M?1 and (7.5±0.5)·104M?1, at 15°C and 25°C, respectively. The average number of moles of phospholipid bound per mole of glucagon is 4.4±0.6. The isothermal enthalpy of reaction of glucagon with DCPC is ?20.5 kcal/mol of glucagon at 25°C and ?32.5 kcal/mol of glucagon at 15°C. The observed enthalpies can arise from glucagon-induced cyrstallization of the phospholipid, from the non-covalent interactions between the peptide and lipid as well as from the lipid-induced conformational change in the protein. These results demonstrate that, unlike the complexes formed between glucagon and phospholipids which form more stable bilayers, the complex formed between glucagon and DCPC is stable over a wide range of temperatures, including temperatures well above the phase transition. 相似文献
52.
A number of carbobenzoxy-dipeptide-amides raise the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine (stabilizes the bilayer). The potency of the peptides in stabilizing the bilayer phase is Z-Tyr-Leu-NH2= Z-Gly-Phe-NH2>Z-Ser-Leu-NH2>Z-Gly-Leu-NH2>Z-Gly-Gly-NH2. A linear correlation was found between the respective HPLC retention time parameterk for the peptide and the slope of the bilayer stabilization curve determined with model membranes by differential scanning calorimetry. One dipeptide, Z-Ser-Leu-NH2, reduces measles virus cytopathic effect (CPE) in Vero cells. The mechanism by which this peptide reduces the CPE is not known, although some peptides which raise the bilayer to hexagonal phase transition temperature of phospholipids inhibit membrane fusion.Abbreviations Z
carbobenzoxy
- DEPE
dielaidoylphosphatidylethanolamine
- DSC
differential scanning calorimetry
- HPLC
high pressure liquid chromatography
- CPE
cytopathic effect
To whom correspondence should be addressed. 相似文献
53.
The basic protein of myelin can spontaneously associate with the synthetic phospholipid N-palmitoylsphingosinephosphatidylcholine. The protein alters the phase transition properties of the lipid from a single transition at 41.5°C to two overlapping transitions, one being slightly above and the other slightly below the transition temperature of the pure lipid. The effect was not seen upon the addition of poly(l-lysine) to this lipid nor does the myelin basic protein alter the phase transition properties of dimyristoylphosphatidylcholine. The results thus demonstrate that the myelin basic protein can interact with a major zwitterionic lipid component of myelin in addition to acidic phospholipids. 相似文献
54.
Diacylglycerols, lysolecithin, or hydrocarbons markedly alter the bilayer to hexagonal phase transition temperature of phosphatidylethanolamines 总被引:11,自引:0,他引:11
R M Epand 《Biochemistry》1985,24(25):7092-7095
The bilayer to hexagonal phase transition temperatures of dielaidoylphosphatidylethanolamine and 1-palmitoyl-2-oleoylphosphatidylethanolamine are 65.6 and 71.4 degrees C, respectively. Using high-sensitivity differential scanning calorimetry, I have shown that these transition temperatures are extremely sensitive to the presence of small amounts of other lipid components. For example, at a mole fraction of only 0.01, dilinolenin lowers the bilayer to hexagonal phase transition temperature of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine by 8.5 degrees C. Other diacylglycerols have similar effects on this transition temperature, although the degree of unsaturation of the acyl chains has some effect, with distearin being less potent. In comparison, the 20-carbon alkane eicosane lowers this transition temperature by 5 degrees C, while palmitoyl-lysolecithin raises it by 2.5 degrees C. Similar effects of these additives on the bilayer to to hexagonal phase transition temperature are observed with dielaidoylphosphatidylethanolamine. At these concentrations of additive, there is no effect on the gel-state to liquid-crystalline-state transition temperature. The observed shifts in the temperature of the bilayer to the hexagonal phase transition can be qualitatively interpreted in terms of the effects of these additives on the hydrophilic surface area and on the hydrophobic volume. Substances expanding the hydrophobic domain promote hexagonal phase formation and lower the bilayer to hexagonal phase transition temperature. The sensitivity of the bilayer to hexagonal phase transition temperature to the presence of additives is at least as great as that which has been observed for any other lipid phase transition. 相似文献
55.
C R Lancaster P K Mishra D W Hughes S A St-Pierre A A Bothner-By R M Epand 《Biochemistry》1991,30(19):4715-4726
The structural requirements for the binding of dynorphin to the kappa-opioid receptor are of profound clinical interest in the search for a powerful nonaddictive analgesic. These requirements are thought to be met by the membrane-mediated conformation of the opioid peptide dynorphin A-(1-13)-peptide, Tyr1-Gly2-Gly3-Phe4-Leu5-Arg6-Arg7-Ile8-Arg9-Pro10- Lys11-Leu12-Lys13. Schwyzer has proposed an essentially alpha-helical membrane-mediated conformation of the 13 amino acid peptide [Schwyzer, R. (1986) Biochemistry 25, 4281-4286]. In the present study, circular dichroism (CD) studies on dynorphin A-(1-13)-peptide bound to an anionic phospholipid signified negligible helical content of the peptide. CD studies also demonstrated that the aqueous-membraneous interphase may be mimicked by methanol. The 500- and 620-MHz 1H nuclear magnetic resonance (NMR) spectra of dynorphin A-(1-13)-peptide in methanolic solution were sequence-specifically assigned with the aid of correlated spectroscopy (COSY), double-quantum filtered phase-sensitive COSY (DQF-COSY), relayed COSY (RELAY), and nuclear Overhauser enhancement spectroscopy (NOESY). 2-D CAMELSPIN/ROESY experiments indicated that at least the part of the molecule from Arg7 to Arg9 was in an extended or beta-strand conformation, which agreed with deuterium-exchange and temperature-dependence studies of the amide protons and analysis of the vicinal spin-spin coupling constants 3JHN alpha. The results clearly demonstrated the absence of extensive alpha-helix formation. chi 1 rotamer analysis of the 3J alpha beta demonstrated no preferred side-chain conformations. 相似文献
56.
The phase behavior of mixtures of cholesterol or epicholesterol with phosphatidylethanolamine was studied by differential scanning calorimetry and by X-ray diffraction. Discrete domains of cholesterol are detected by X-ray diffraction in the L alpha phase of phosphatidylethanolamine from egg yolk and synthetic dielaidoylphosphatidylethanolamine beginning at mole fractions of 0.35-0.4 cholesterol. Separate domains of crystalline epicholesterol can also be detected in the L alpha phase of dielaidoylphosphatidylethanolamine by X-ray diffraction at as little as 0.16 mole fraction of epicholesterol. This is a result of poor miscibility of the epicholesterol with dielaidoylphosphatidylethanolamine. Epicholesterol does not alter the L beta----L alpha transition or bilayer spacing. Epicholesterol also has little effect on the diameter of the cylinders in the hexagonal phase. Formation of the inverted hexagonal phase is facilitated by addition of small amounts of cholesterol (mole fraction less than 0.2) in both egg phosphatidylethanolamine and dielaidoylphosphatidylethanolamine. However, at higher mole fractions of cholesterol, the stability of the liquid-crystalline phase is found to increase markedly for dielaidoylphosphatidylethanolamine but not for egg phosphatidylethanolamine, indicating the importance of the structure of the acyl chains in controlling the relative stability of the lamellar and nonlamellar phases in these systems. In contrast to cholesterol, epicholesterol markedly lowers the L alpha----HII phase transition temperature at low mole fraction of sterol. This result demonstrates the importance of the orientation and motional properties of an additive in determining the L alpha----HII transition temperature. 相似文献
57.
58.
We have assessed the biological activity of salmon calcitonin I (sCT) using an in vivo biological assay of hypocalcemic activity in rats. The changes in biological activity observed are explained on the basis of changes in the conformational properties of the hormone analogues. Helical content in the presence and absence of lipids and detergents was assessed by using circular dichroism, and the section of the molecule that folds into a helix was predicted on the basis of the helix-coil transition theory of Mattice and co-workers. In the amino acid sequence of sCT, residue 8 is valine and residue 16 is leucine. The synthetic calcitonin derivatives [Gly8]sCT and [Ala16]sCT have higher biological activity than the native hormone although they have a lower helical content. The increased biological activity of these derivatives is ascribed to an increase in their conformational flexibility resulting from the substitution of amino acid residues with less bulky side chains and less tendency to form helical structures. The derivative [Met8]sCT has less substitution than sCT on the beta-carbon at position 8, but it has increased helix-forming potential in the region of residues 8-12. These two factors affect conformational flexibility in opposite ways, resulting in the biological activity of [Met8]sCT being slightly higher than that of sCT. However, increased conformational flexibility does not always increase biological activity. Substitution of the L-arginine at residue 24 for a D-arginine has little effect on the conformational properties or biological activity of sCT. However, [Gly8, D-Arg24]sCT is less active than sCT, [Gly8]sCT, or [D-Arg24]sCT.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
59.
60.
The phase behaviour of 1-palmitoyl-2-oleoylphosphatidylethanolamine (POPE) was studied by differential scanning calorimetry and 31P-NMR spectroscopy. Modulation of the phase behaviour of POPE by 1-palmitoyl-2-oleoylphosphatidylserine (POPS). 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), 1,2-di-olein (DOG), CaCl2, MgCl2, and combinations of these substances was studied. The bilayer-forming lipids, POPS and POPC, raise the bilayer-to-hexagonal phase-transition temperature of POPE. The POPC has a greater effect than POPS, probably because the former lipid is more miscible with POPE. Addition of 10 mM CaCl2 has little effect on the phase-transitions of POPE/POPC mixtures, but it greatly decreases the effectiveness of POPS in raising the bilayer-to-hexagonal phase-transition temperature of POPE. The effectiveness of DOG in lowering the phase-transition temperature of POPE is also greatly reduced in the presence of 10 mM CaCl2. This phenomenon may play a role in the negative feedback regulation of protein kinase C. 相似文献