PMID: 8590755Nov 1, 1995

Spectroscopic study of the mechanism of cholesterol interaction with apolipoproteins: a model of cholesterol-synthetic apolipoprotein A-I fragment

Biokhimii︠a︡
A N KlimovSh S Shaiakhmedov

Abstract

To investigate the mechanism of cholesterol binding to apolipoproteins, a fragment of human apolipoprotein A-I involving its amino acid residues 144-164 has been synthesized. The interaction of this peptide (both native and having modified functional groups) with cholesterol in a water-alcohol medium has been studied, using fluorescence and circular dichroism techniques as well as NMR NOE spectroscopy. It has been found that the oligopeptide is able to form complexes with one and two cholesterol molecules, the association constant being as high as 10(8) M-1. The interaction involves hydrogen bonds formed by the cholesterol OH-group as well as hydrophobic interaction of the nonpolar groups of cholesterol and the peptide. The latter requires a specific conformation, i.e., the formation in the peptide molecule of a "cavity" at the expense of ionic coupling between the carboxylate groups in Asp or Glu side chains and the guanidinium groups of the protein. At pH 6.3, the OH-group of cholesterol becomes involved in the H-bond system which includes a COOH-group of Asp and two imidazole groups of His, one of which is in a neutral and the other one in a protonated from.

Related Concepts

Epicholesterol
Circular Dichroism, Vibrational
Hydrogen Bonding
In Vivo NMR Spectroscopy
Fluorescence Spectroscopy
Spectrophotometry, Ultraviolet
Pro-Apolipoprotein A-I

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