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The major protein of high density llpoproteln (HDL), apolipoprotein (apo) A-l, is the major activator of the plasma enzyme lecithin:cholesterol acyltransferase (LCAT). A consensus amlno acid sequence has been defined for the eight, 22-resldue long, tandem amphlpathic helical repeats located in the carboxy-terminal region of apo A-l. A series of 22 and 44mer synthetic peptide analogues of the consensus domain, differing only In their 13th amlno acid residue, were prepared and tested for LCAT activation. One of the peptldes was found to equal apo A-l In LCAT activation. This is the first time a peptide activator for LCAT that rivals the activity of apo A-l in the vesicular and discoldal egg phosphatidylcholine assay systems has been synthesized. Based on these results, we propose that the major LCAT-actlvating domain of apo A-l resides in the 22mer tandem repeats, each containing Glu at the 13th residue and located between residues 66 and 121 In the native apolipoprotein.
Arteriosclerosis – Wolters Kluwer Health
Published: Jan 1, 1990
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