Abnormal lecithin:cholesterol acyltransferase activation by a human apolipoprotein A-I variant in which a single lysine residue is deleted

J Biol Chem. 1984 Aug 25;259(16):10063-70.


An apolipoprotein (apo) A-I variant that has a relative charge of -1 compared to normal apo-A-I on isoelectric focusing gels has been identified in five unrelated families as a result of screening a large number of individuals. The cause of the electrophoretic abnormality has been examined by analyzing the variant apo-A-I structure. The evidence suggests that a single amino acid, lysine 107, has been deleted in the variant apo-A-I of all affected individuals studied from these families, with the remainder of the variant apo-A-I sequence being unaffected. The deletion of this single basic amino acid residue is sufficient to account for the charge difference between the variant and normal apo-A-I as seen on isoelectric focusing gels. This variant, previously referred to as A-I-Marburg or A-I-Münster-2, can now be designated by the structural abnormality apo-A-I(Lys107----0). The evidence from extensive pedigree analysis suggests the likelihood that the deletion mutant gene is allelic to the normal apo-A-I gene. At the same time, the kindred analyses have failed to yield a lipid abnormality that can be unequivocally related to the presence of this deletion mutant of apo-A-I. However, all subjects expressing apo-A-I(Lys107----0) also express normal apo-A-I, so that any abnormality caused by the variant apo-A-I might be adequately compensated for by the normal apo-A-I. To examine directly the functional consequence of the lysine deletion, the isolated variant was tested in vitro for its ability to activate lecithin:cholesterol acyltransferase, the principal cholesterol-esterifying enzyme in plasma. It was found that apo-A-I(Lys107----0) is deficient in its ability to activate lecithin:cholesterol acyltransferase, having only 40-60% of the cofactor activity of normal apo-A-I. The cofactor activity of the pro-apo-A-I component of the variant was also reduced to about 60% of either normal A-I or normal pro-apo-A-I. The functional defect is probably related to a disruption in the secondary and/or tertiary structure of the protein caused by the deletion of lysine 107 in the primary structure.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amino Acids / analysis
  • Apolipoprotein A-I
  • Apolipoproteins / genetics*
  • Chromosome Deletion
  • Enzyme Activation
  • Female
  • Genetic Variation*
  • Humans
  • Lipoproteins, HDL / genetics*
  • Lysine*
  • Male
  • Middle Aged
  • Pedigree
  • Peptide Fragments / analysis
  • Phosphatidylcholine-Sterol O-Acyltransferase / metabolism*
  • Protein Conformation


  • Amino Acids
  • Apolipoprotein A-I
  • Apolipoproteins
  • Lipoproteins, HDL
  • Peptide Fragments
  • Phosphatidylcholine-Sterol O-Acyltransferase
  • Lysine