Apolipoprotein AIMilano. Accelerated binding and dissociation from lipids of a human apolipoprotein variant.
The lipid binding properties of apolipoprotein (apo) AIMilano, a molecular variant of human apolipoprotein AI, characterized by the Arg173----Cys substitution, was investigated by the use of dimyristoylphosphatidylcholine liposomes. Both the variant AIMilano and normal AI are incorporated to the same extent in stable complexes isolated by gel filtration, showing similar dimensions and stoichiometries. A higher affinity of apo-AIMilano for dimyristoylphosphatidylcholine is suggested by the faster association rate of the variant apoprotein compared to normal AI; similarly, apo-AIMilano is more readily displaced by guanidine hydrochloride from the isolated dimyristoylphosphatidylcholine-apoprotein complexes. When the secondary structure of apo-AIMilano was investigated by spectrofluoroscopy and circular dichroism, a higher fluorescence peak wavelength and a lower alpha-helical content were detected in the variant apoprotein compared to normal AI. The substitution Arg173----Cys in the AIMilano dramatically alters the amphipathic nature of the modified alpha-helical fragment of apoprotein AI. The association rate with lipids is accelerated by an increased exposure of hydrophobic residues. The reduced stability of the lipid-apoprotein particles is possibly mediated by a reduction in the number of helical segments involved in lipid association. The high flexibility of the AIMilano apolipoprotein in the interaction with lipids may explain its accelerated catabolism and the possibly improved uptake capacities for tissue lipids.
D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000097:blood* / Q000235:genetics / Q000302:isolation & purification; D002942:Circular Dichroism; D014644:Genetic Variation; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood*; D011485:Protein Binding; D011487:Protein Conformation
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D008075:Lipoproteins, HDL