Apolipoprotein A‐IGiessen (Pro143→Arg)

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Abstract
Apolipoprotein A‐IGiessen is a variant form of apo A‐I that is displaced from the corresponding normal A‐I isoforms on isoelectric focusing gels by a single charge unit towards the cathode [Utermann et al. (1982) J. Biol. Chem. 257, 501–507]. Three subjects heterozygous for the variant were detected in one family. The percentage of the total A‐I in plasma represented by the A‐IGiessen in these subjects ranged over 25–30%. The variant and normal major A‐I isoforms from the proband (Y.J.) were purified by preparative isoelectric focusing and cleaved with CNBr. Analytical focusing of CNBr fragments demonstrated a charge difference between CB3Giessen and normal CB3. Sequence analysis of CB3Giessen revealed that a proline existing in normal A‐I was replaced by an arginine in the variant A‐I at residue 143. The ability of the mutant A‐I to activate purified lecithin:cholesterol acyltransferase was determined in vitro. The cofactor activity of [Arg143]apolipoprotein A‐I was about 60–70% of that demonstrated by control A‐I. Residue 143 is in a putative β‐turn between two of the repeating amphiphilic helices in apolipoprotein A‐I and may be a critical determinant of the protein's structure and function.