Activation of lecithin:cholesterol acyltransferase by a synthetic model lipid-associating peptide.
We have synthesized a model lipid-associating peptide of 20 residues (LAP-20) and studied its association with the phospholipid dimyristoyl phosphatidylcholine (DMPC) and its activation of the plasma enzyme lecithin:cholesterol acyl-transferase (EC 2.3.1.43). The lipid-associating behavior of LAP-20 is similar to that of well-characterized native plasma apolipoproteins after which it was modeled. Upon forming an isolated complex with DMPC, LAP-20 exhibits a large blue-shift in its intrinsic fluorescence, converts from a random coil to an alpha -helix, and changes turbid multilamellar structures of DMPC into small complexes that are optically clear. Addition of 2 mol % cholesterol does not detectably alter the structure or properties of the complex. The cholesterol-containing complexes of LAP-20 and DMPC are substrates for LCAT, having an activity 65% of that of complexes composed of DMPC, cholesterol, and the natural activator, apolipoprotein A-I. These findings suggest that the LCAT-activating regions of apoA-I may be confined to relatively short sequences that contain a lipid-binding determinant.
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D055598:Chemical Phenomena; D002621:Chemistry; D002784:Cholesterol; D002850:Chromatography, Gel; D002942:Circular Dichroism; D004134:Dimyristoylphosphatidylcholine; D004789:Enzyme Activation; D008956:Models, Chemical; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D010713:Phosphatidylcholines; D013050:Spectrometry, Fluorescence; D013696:Temperature
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D010455:Peptides; D010713:Phosphatidylcholines; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D004134:Dimyristoylphosphatidylcholine