Apolipoprotein A-IGiessen (Pro143----Arg). A mutant that is defective in activating lecithin:cholesterol acyltransferase.
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 beta-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.
D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000097:blood* / Q000235:genetics; D055598:Chemical Phenomena; D002621:Chemistry; D003067:Coenzymes; D003488:Cyanogen Bromide; D004586:Electrophoresis / Q000379:methods; D004789:Enzyme Activation; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007525:Isoelectric Focusing; D009154:Mutation; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D003067:Coenzymes; C043360:apolipoprotein A-I Giessen; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D003488:Cyanogen Bromide