title: Activation of lipoprotein lipase by native and synthetic fragments of human plasma apolipoprotein C-II.
abstract: Apolipoprotein C-II (apoC-II), a protein constituent of human very low density lipoproteins, is the activator for lipoprotein lipase (LPL; triacylglycerol acyl-hydrolase, EC 3.1.1.3). The amino acid sequence of the 78 residues of apoC-II has recently been established in this laboratory. To determine the minimal sequence requirements for activation, we have prepared both native and synthetic fragments of apoC-II and tested them for their ability to activate LPL. Cyanogen bromide fragments of apoC-II corresponding to residues 1--9 and 10--59 had little ability to activate LPL. However, the COOH-terminal cyanogen bromide fragment corresponding to residues 60--78 increased hydrolysis 4-fold compared to an average of 9-fold activation for the same concentration of apoC-II. The synthetic peptide containing residues 60--78 prepared by solid-phase techniques enhanced the lipolysis 3-fold. Addition of five residues produced a synthetic fragment 55--78 that enhanced the release of fatty acid 12-fold compared to 13-fold for intact apoC-II. By contrast, the synthetic peptide containing residues 66--78 did not activate. Removal of the three COOH-terminal residues, Gly-Glu-Glu, from fragment 60--78 decreased the ability to activate LPL by greater than 95%. These studies suggest that the maximal activation of LPL by apoC-II requires a minimal sequence contained within residues 55--78.
mesh_terms: D000595:Amino Acid Sequence; D001053:Apolipoproteins / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D003488:Cyanogen Bromide; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006858:Hydrofluoric Acid; D006868:Hydrolysis; D008071:Lipoprotein Lipase / Q000378:metabolism*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D001053:Apolipoproteins; D010446:Peptide Fragments; D008071:Lipoprotein Lipase; D003488:Cyanogen Bromide; D006858:Hydrofluoric Acid
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