title: Thermodynamics of the binding of human apolipoprotein A-I to dimyristoylphosphatidylglycerol.
abstract: The interaction of human serum apolipoprotein A-I with dimyristoylphosphatidylglycerol was analyzed by isothermal titration calorimetry. Binding of the apolipoprotein A-I to large unilamellar vesicles of dimyristoylphosphatidylglycerol, a negatively charged phospholipid, is characterized by thermodynamic parameters which are invariant over the 30-40 degrees C temperature range. The enthalpy change resulting from the first additions of lipid are positive and decline in magnitude with subsequent additions of lipid. After several additions of lipid, the sign of the enthalpy changes to negative and then reaches a constant value/injection. This exothermic process is larger and opposite in sign to the heat of dilution. Similar behavior is also observed when the lipid is in the form of a dispersion in distilled water. Only a non-saturable exothermic process is observed at 30 degrees C with large unilamellar vesicles of the zwitterionic lipid, dimyristoylphosphatidylcholine. The beginning of an exothermic process can also be observed prior to the larger endotherm in the first injections of large unilamellar vesicles of dimyristoylphosphatidylglycerol into the protein. We analyze the enthalpy changes for the reaction of dimyristoylphosphatidylglycerol with the protein as arising from two distinct processes, one endothermic and the other exothermic. The binding isotherms for the high affinity binding of the apolipoprotein A-I to large unilammelar vesicles of dimyristoylphosphatidylglycerol, over the temperature range 30-40 degrees C, gave an enthalpy change of 1.43 +/- 0.07 kcal/mol of protein and a free energy change of -5.91 +/- 0.04 kcal/mol of protein for the binding of the protein to a cluster of 25 +/- 2 lipid molecules. Thus this reaction is entropically driven.
authors.affiliation: Department of Biochemistry, McMaster University Health Sciences Center, Hamilton, Ontario, Canada.
authors.forename: R M
authors.initials: RM
authors.lastname: Epand
authors.forename: J P
authors.initials: JP
authors.lastname: Segrest
authors.forename: G M
authors.initials: GM
authors.lastname: Anantharamaiah
mesh_terms: D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000097:blood*; D002151:Calorimetry; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood*; D010715:Phosphatidylglycerols / Q000378:metabolism*; D011485:Protein Binding; D013816:Thermodynamics
chemical_list: D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D008075:Lipoproteins, HDL; D010715:Phosphatidylglycerols; C002773:dimyristoylphosphatidylglycerol