Reconstituted high-density lipoproteins with a disulfide-linked apolipoprotein A-I dimer: Evidence for restricted particle size heterogeneity

Laura Calabresi, Giuseppe Vecchio, Francesco Frigerio, Laura Vavassori, Cesare R. Sirtoi, Guido Franceschini

Research output: Contribution to journalArticle

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Abstract

The apolipoprotein A-I(Milano) (apoA-I(M)) is a molecular variant of apoA-I characterized by the Arg173→Cys substitution, resulting in the formation of homodimers (A-I(M)/A-I(M)) and heterodimers with apoA-II. In order to examine the effects of the introduction of an interchain disulfide bridge on the lipid-binding properties of apoA-I, the present studies compare the kinetics of association of A-I(M)/A-I(M) and apoA-I with dimyristoylphosphatidylcholine (DMPC), and the structure and properties of reconstituted HDL containing palmitoyloleoylphosphatidylcholine (POPC) and either A-I(M)/A-I(M) or apoA-I. The results show that apoA-I dimerization does not affect the rate of association with DMPC. Apolipoprotein-POPC complexes instead, when analyzed by nondenaturing gradient gel electrophoresis, demonstrate that, differently from apoA-I, A-I(M)/A-I(M) forms only two species of rHDL particles despite a wide range of initial lipid to protein ratios. These two rHDL species contain one or two A-I(M)/A- I(M) molecules and have a diameter of 7.8 nm and 12.5 nm. Investigations of the A-I(M)/A-I(M) structure in these two rHDL, by circular dichroism, fluorescence, and second-derivative UV spectroscopy, suggest that the secondary and tertiary structures of A-I(M)/A-I(M) re remarkably similar in both small and large particles. These results suggest that the introduction of an interchain disulfide bridge does not affect the association of apoA-I with lipids but restricts HDL particle size heterogeneity, thus possibly affecting HDL function in lipid metabolism and atherosclerosis protection.

Original languageEnglish
Pages (from-to)12428-12433
Number of pages6
JournalBiochemistry
Volume36
Issue number41
DOIs
Publication statusPublished - Oct 14 1997

Fingerprint

Apolipoprotein A-I
HDL Lipoproteins
Particle Size
Disulfides
Dimers
Particle size
Dimyristoylphosphatidylcholine
Association reactions
Lipids
Apolipoprotein A-II
Dimerization
Apolipoproteins
Circular Dichroism
Electrophoresis
Ultraviolet spectroscopy
Lipid Metabolism
Spectrum Analysis
Atherosclerosis
Substitution reactions
Fluorescence

ASJC Scopus subject areas

  • Biochemistry

Cite this

Calabresi, L., Vecchio, G., Frigerio, F., Vavassori, L., Sirtoi, C. R., & Franceschini, G. (1997). Reconstituted high-density lipoproteins with a disulfide-linked apolipoprotein A-I dimer: Evidence for restricted particle size heterogeneity. Biochemistry, 36(41), 12428-12433. https://doi.org/10.1021/bi970505a

Reconstituted high-density lipoproteins with a disulfide-linked apolipoprotein A-I dimer : Evidence for restricted particle size heterogeneity. / Calabresi, Laura; Vecchio, Giuseppe; Frigerio, Francesco; Vavassori, Laura; Sirtoi, Cesare R.; Franceschini, Guido.

In: Biochemistry, Vol. 36, No. 41, 14.10.1997, p. 12428-12433.

Research output: Contribution to journalArticle

Calabresi, L, Vecchio, G, Frigerio, F, Vavassori, L, Sirtoi, CR & Franceschini, G 1997, 'Reconstituted high-density lipoproteins with a disulfide-linked apolipoprotein A-I dimer: Evidence for restricted particle size heterogeneity', Biochemistry, vol. 36, no. 41, pp. 12428-12433. https://doi.org/10.1021/bi970505a
Calabresi, Laura ; Vecchio, Giuseppe ; Frigerio, Francesco ; Vavassori, Laura ; Sirtoi, Cesare R. ; Franceschini, Guido. / Reconstituted high-density lipoproteins with a disulfide-linked apolipoprotein A-I dimer : Evidence for restricted particle size heterogeneity. In: Biochemistry. 1997 ; Vol. 36, No. 41. pp. 12428-12433.
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