Apolipoprotein AIMilano. Accelerated binding and dissociation from lipids of a human apolipoprotein variant.
Year: 1985
Type: article
Abstract: The lipid binding properties of apolipoprotein (apo) AIMilMo, a molecular variant of human apolipoprotein AI, characterized by the Arg173 e Cys substitution, was investigated by the use of dimyristoylphosphatidylcholine liposomes.Both the variant AIM^^,, 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-AIMihO for dimyristoylphosphatidylcholine is suggested by the faster association rate of the variant apoprotein compared to normal AI; similarly, apo-AIMiI,, is more readily displaced by guanidine hydrochloride from the isolated dimyristoylphosphatidylcholine-apoprotein complexes.When the secondary structure of apo-AI~lm,, was investigated by spectrofluoroscopy and circular dichroism, a higher fluorescence peak wavelength and a lower a-helical content were detected in the variant apoprotein compared to normal AI.The substitution Arg1'3 .-,Cys in the dramatically alters the amphipathic nature of the modified a-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.Human apolipoprotein AI is the major protein constituent of plasma high density lipoproteins.HDL* play a critical role in the process of cholesterol transport from tissues to plasma and a significant correlation has been detected in clinical and epidemiological studies between low plasma apo-AI and HDL cholesterol and increased risk of premature cardiovascular disease (1,2).Apo-AI is a single polypeptide chain, composed of 243 amino acids (3), and can interact with different phos-* This work was supported in part by Grant 1 RO1 HL28961-01 awarded by the National Heart, Lung and Blood Institute and by the Consiglio Nazionale delle Ricerche of Italy (PF Ingegneria Genetica e Basi Malecolari delle Malattie Ereditarie).The costs of publication of this article were defrayed in part by the payment of page charges.This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.Section 1734 solely to indicate this fact.
Source: Journal of Biological Chemistry
Authors: G Franceschini, G Vecchio, G Gianfranceschi, D Magani, C R Sirtori
Institutions: University of Milan, National Research Council
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W71984142