Apolipoprotein A-I(Milano) is a molecular variant of apoA-I, containing the Arg173→Cys substitution that forms a disulfide linked homodimer (A-I(M)/A-I(M)). To assess the effect of this structural modification on a major function of the apolipoprotein, its activation of lecithin cholesterol acyltransferase (LCAT), we prepared well-defined complexes of A-I(M)/A-I(M) and apoA-I with phospholipids and cholesterol and compared their reactivities with LCAT. Particles with A-I(M)/A-I(M) had very similar diameters to apoA-I particles (7.8 and 12.5 nm) but had distinct apolipoprotein and phospholipid contents and protein secondary structures; they bound LCAT with comparable affinities, but were less efficient substrates for the enzyme (40 to 70% less reactive). We conclude that the local structural constraints in A-I(M)/A-I(M) do not prevent the formation of well-defined complexes with phospholipids and do not influence the binding of the enzyme to the particles, but have an inhibitory effect on LCAT activation.

Activation of lecithin cholesterol acyltransferase by a disulfide-linked apolipoprotein A-I dimer / L. Calabresi, G. Franceschini, A. Burkybile, A. Jonas. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - 232:2(1997), pp. 345-349.

Activation of lecithin cholesterol acyltransferase by a disulfide-linked apolipoprotein A-I dimer

L. Calabresi
Primo
;
G. Franceschini
Secondo
;
1997

Abstract

Apolipoprotein A-I(Milano) is a molecular variant of apoA-I, containing the Arg173→Cys substitution that forms a disulfide linked homodimer (A-I(M)/A-I(M)). To assess the effect of this structural modification on a major function of the apolipoprotein, its activation of lecithin cholesterol acyltransferase (LCAT), we prepared well-defined complexes of A-I(M)/A-I(M) and apoA-I with phospholipids and cholesterol and compared their reactivities with LCAT. Particles with A-I(M)/A-I(M) had very similar diameters to apoA-I particles (7.8 and 12.5 nm) but had distinct apolipoprotein and phospholipid contents and protein secondary structures; they bound LCAT with comparable affinities, but were less efficient substrates for the enzyme (40 to 70% less reactive). We conclude that the local structural constraints in A-I(M)/A-I(M) do not prevent the formation of well-defined complexes with phospholipids and do not influence the binding of the enzyme to the particles, but have an inhibitory effect on LCAT activation.
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/187885
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