title: Interaction of alpha-melanocyte stimulating hormone with binary phospholipid membranes: structural changes and relevance of phase behavior.
abstract: The interaction of alpha-melanocyte stimulating hormone (alpha-MSH) with negatively charged binary membrane systems composed of either 1,2-dimyristoyl-sn-glycero-3-phosphocholine/1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)], (DMPC/DMPG) or DMPC/1,2-dimyristoyl-sn-glycero-3-phosphate (DMPC/DMPA), both at a 3:1 ratio, was studied using complementary techniques (differential scanning calorimetry, infrared and ultraviolet absorption spectroscopy, and steady-state and time-resolved fluorescence). The peptide structure in buffer, at medium to high concentrations, is a mixture of aggregated beta-strands and random coil, and upon increasing the temperature the random coil configuration becomes predominant. At low concentrations (micromolar) there are essentially no aggregates. When in interaction with the lipidic systems this transition is prevented and the peptide is stabilized in a specific conformation different from the one in solution. The incorporation of alpha-MSH into phosphatidic acid-containing systems produced a significant alteration of the calorimetric data. Lateral heterogeneity can be induced by the peptide in the DMPA-containing mixture, at variance with the one of DMPG. In addition, the lipid/water partition coefficient for the peptide in the presence of DMPC/DMPA is greater in the gel phase as compared to the fluid phase. From the high values of limiting anisotropies it can be concluded that the peptide presents a very reduced rotational dynamics when in interaction with the lipids, pointing out to a strong interaction. Overall, these results show that the structure and stability of alpha-MSH in a negatively charged membrane environment are substantially different from those of the peptide in solution, being stabilized in a specific conformation that could be important to eliciting its biological activity.
authors.affiliation: Centro de Biología Molecular y Celular, Universidad Miguel Hernández, E-03206 Elche-Alicante, Spain.
authors.forename: L M
authors.initials: LM
authors.lastname: Contreras
authors.forename: R F
authors.initials: RF
authors.lastname: de Almeida
authors.forename: J
authors.initials: J
authors.lastname: Villalaín
authors.forename: A
authors.initials: A
authors.lastname: Fedorov
authors.forename: M
authors.initials: M
authors.lastname: Prieto
mesh_terms: D055592:Biophysical Phenomena; D001703:Biophysics; D002152:Calorimetry, Differential Scanning; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D007700:Kinetics; D008055:Lipids / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D013997:Time Factors; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry; D000521:alpha-MSH / Q000737:chemistry*
chemical_list: D008055:Lipids; D009943:Organophosphorus Compounds; D010715:Phosphatidylglycerols; D010743:Phospholipids; D014867:Water; C073636:cyclohexyl methylphosphonic acid; D000521:alpha-MSH; C002773:dimyristoylphosphatidylglycerol; D004134:Dimyristoylphosphatidylcholine