Environmental Engineering Reference
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Folding of the Apolipoprotein
A1 Driven by the Salt Concentration
as a Possible Mechanism to Improve
Cholesterol Trapping
M.A. Balderas Altamirano, A. Gama Goicochea and E. Pérez
Abstract
The folding of the cholesterol—trapping apolipoprotein A1 in aqueous
solution at increasing ionic strength—is studied using atomically detailed molecular
dynamics simulations. We calculate various structural properties to characterize the
conformation of the protein, such as the radius of gyration, the radial distribution
function and the end-to-end distance. Additionally we report information using tools
specifically tailored for the characterization of proteins, such as the mean smallest
distance matrix and the Ramachandran plot. We find that two qualitatively different
configurations of this protein are preferred: one where the protein is extended, and
one where it forms loops or closed structures. It is argued that the latter promote the
association of the protein with cholesterol and other fatty acids.
1 Introduction
The apolipoprotein A1 (APOA1) is the main component of high-density lipoproteins
and has an important role in lipid metabolism. APOA1 is found in the human blood
stream and promotes fatty acid efflux, including cholesterol, from tissues to the
liver for excretion. Its study is important because of its protective effect against
atherosclerosis (Breslow
1996
) and its function as a cholesterol transport from white
blood cells within artery walls (Glomset
1968
). APOA1 contains a single polypeptide
chain of 243 amino acid residues (Brewer et al.
1978
) with 11 or 22 regularly repeating
residues in the sequence (McLachlan
1977
). These multiple repeating units were
proposed to form amphipathic helices with distinct hydrophilic and hydrophobic
faces (Segrest et al.
1974
). The fat transport is then expected to be modulated by
the hydrophilic and hydrophobic residues along APOA1, but also by physiological
conditions like pH and ionic strength in the blood or physiological fluid.
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