Lecithin:cholesterol acyltransferase activation and lipid binding by synthetic fragments of apolipoprotein C-I.

Peptide fragments of apolipoprotein C-I (apoLP-C-I) have been synthesized by solid phase methodology. After purification, each peptide showed the correct amino acid analysis and was a single band by polyacrylamide gel electrophoresis. In density gradient ultracentrifugation with vesicles of dimyristoyl phosphatidylcholine, peptide fragments 32-57, 24-57, and 17-57 formed stable complexes while 39-57 did not. With mixed vesicles of dimyristoyl phosphatidylcholine-cholesterol 20 micrometer of the fragments 32-57, 24-57 and 17-57 stimulated lecithin:cholesterol acyltransferase (LCAT) activity 50, 60, and 100%, respectively, of the value found for apolipoprotein C-I, while fragment 39-57 was inactive. The results indicate that residues 17-57 contain the structural requirements for LCAT activation by apoLP-C-I, and that residues 32-57 represent one of the major phospholipid-binding regions of apoLP-C-I.