title: Effect of pH-variation on insertion and ion channel formation of human calcitonin into planar lipid bilayers.
abstract: Human calcitonin is the physiological hormone involved in calcium-phosphorus homeostasis. However, its use is limited by its propensity to form aggregates. We find that the type of host lipid has a pronounced influence on human calcitonin fibrillation or incorporation, as assessed by channel formation, in planar lipid membranes at neutral pH. At pH 7, human calcitonin is able to interact and form channels with negatively charged dioleoyl-phosphatidylglycerol (DOPG) bilayers and with zwitterionic palmitoyl-oleoyl phosphatidylcholine (POPC) bilayers containing 15% negatively-charged DOPG, but not with POPC bilayers. At low pH (4.5 and 3.8), the conformational variation of the peptide enables it to insert into POPC and POPC:DOPG but not into DOPG bilayers. The model proposed for human calcitonin interaction and channel formation at acidic pH was based on theoretical predictions of the protonation-deprotonation state of some amino acids, in particular in the fibrillating sequence of peptide molecules; the length of the alpha-helix, and the electrostatic and/or hydrophobic interaction also seem to be relevant. These results may suggest that human calcitonin at low local pH could be involved in osteoclasts' calcium-sensitive permeability through channel formation and/or receptor interaction.
authors.affiliation: Dept. Farmaco-Biologico, Università degli Studi di Bari, I-70126 Bari, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Micelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Meleleo
authors.forename: Vittorio
authors.initials: V
authors.lastname: Picciarelli
authors.forename: Enrico
authors.initials: E
authors.lastname: Gallucci
mesh_terms: D002116:Calcitonin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism*; D010010:Osteoclasts / Q000502:physiology; D010539:Permeability; D010713:Phosphatidylcholines / Q000378:metabolism*; D017433:Protein Structure, Secondary; D015398:Signal Transduction
chemical_list: D007473:Ion Channels; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D002116:Calcitonin; C017251:1,2-oleoylphosphatidylcholine; D002118:Calcium