Open AccessActivation of lecithin:cholesterol acyltransferase by a synthetic model lipid-associating peptide.
Author(s) -
Henry J. Pownall,
Angela S. Hu,
Antonio M. Gotto,
John J. Albers,
James T. Sparrow
Publication year - 1980
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.77.6.3154
Subject(s) - chemistry , phospholipid , phosphatidylcholine , lecithin , cholesterol , sterol o acyltransferase , apolipoprotein b , peptide , enzyme , biochemistry , activator (genetics) , stereochemistry , biophysics , lipoprotein , biology , membrane , gene
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.