TY - JOUR
T1 - Thermodynamics of lipid-protein association and the activation of lecithin:Cholesterol acyltransferase by synthetic model apolipopeptides
AU - Pownall, Henry J.
AU - Gotto, Antonio
AU - Sparrow, James T.
PY - 1984/4/18
Y1 - 1984/4/18
N2 - We have synthesized three lipid-associating peptides of 16, 20 and 24 residues (LAP-16, -20, -24, respectively) and measured their affinities for the synthetic lipid, dimyristoylphosphatidylcholine (DMPC) and their activation of the enzyme, lecithin:cholesterol acyltransferase (EC 2.3.1.43). All three, to varying degrees, have many of the physical properties of native apolipoproteins; these include the spontaneous association with DMPC with a concomitant increase in their helical content and transfer of their hydrophobic amino acid residues from the aqueous phase to the less-polar lipid phase. The free energy of association with DMPC, ΔGa, decreases in the order LAP-24 > LAP-20 > LAP-16. Salts such as NaCl increase the lipid-peptide association but guanidine hydrochloride decreases it. These data suggest that the association is largely hydrophobic. LAP-24 self-associates but this process does not compete effectively with the lipid-peptide association. All three peptides activate lecithin:cholesterol acyltransferase if they are associated with the substrate.
AB - We have synthesized three lipid-associating peptides of 16, 20 and 24 residues (LAP-16, -20, -24, respectively) and measured their affinities for the synthetic lipid, dimyristoylphosphatidylcholine (DMPC) and their activation of the enzyme, lecithin:cholesterol acyltransferase (EC 2.3.1.43). All three, to varying degrees, have many of the physical properties of native apolipoproteins; these include the spontaneous association with DMPC with a concomitant increase in their helical content and transfer of their hydrophobic amino acid residues from the aqueous phase to the less-polar lipid phase. The free energy of association with DMPC, ΔGa, decreases in the order LAP-24 > LAP-20 > LAP-16. Salts such as NaCl increase the lipid-peptide association but guanidine hydrochloride decreases it. These data suggest that the association is largely hydrophobic. LAP-24 self-associates but this process does not compete effectively with the lipid-peptide association. All three peptides activate lecithin:cholesterol acyltransferase if they are associated with the substrate.
KW - Apolipoprotein
KW - Lecithin:cholesterol acyltransferase
KW - Lipid-protein interaction
KW - Lipoprotein metabolism
KW - Model peptide
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U2 - 10.1016/0005-2760(84)90316-3
DO - 10.1016/0005-2760(84)90316-3
M3 - Article
AN - SCOPUS:0021261905
VL - 793
SP - 149
EP - 156
JO - Biochimica et Biophysica Acta - Lipids and Lipid Metabolism
JF - Biochimica et Biophysica Acta - Lipids and Lipid Metabolism
SN - 0005-2760
IS - 2
ER -