| The anti-atherosclerotic effect of HDL or its major protein component, apolipoprotein A-I (apoA-I), mainly derives from their key roles in the process of reverse cholesterol transport (RCT). ApoA-I in lipid-free or lipid-poor state is the most efficient acceptors of cellular cholesterols or phosphalipids. The most striking feature of apoA-I is the presence of 8 repeat units of 22- amino acids, forming amphipathic a helix.ApoA-IMilano (apoA-IM) is a naturally occurring mutant of apoA-I, which is characterized by an Arg173 →Cys substitution, resulting in the formation of disulfide-linked homodimers or heterodimers with apoA-II. Studies showed that this mutant seemed to confer to its carriers or experimental animals an increased protection against cardiovascular disease. And the same phenomenon was also shared by another cysteine mutant of apoA-I, named as apoA-IParis (Arg151 → Cys). Structural analysis indicated that both mutants positioned at the polar-nonpolar interface on the a helix.AIM:In this study, we compared the structural and functional properties of wild-type apoA-I (wtapoA-I) and its 7 cysteine substitution mutants, each occurring on a separate amphipathic a helix. Our aim is to explore how the replacement of cysteine influences the structure and function of apoA-I, and whether there is a relationship between the structures and functions of mutants with specific cysteine mutant sites. We hope that our findings could shed some lights on the potential mechanisms of the special cardiovascular protection that apoA-IM presented. METHODS:Seven single cysteine mutants of apoA-I were designed and generated by... |
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