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Biochemistry. 2013 Mar 19;52(11):1963-72. doi: 10.1021/bi400032y. Epub 2013 Mar 4.

Interactions of apolipoprotein A-I with high-density lipoprotein particles.

Author information

1
Lipid Research Group, Gastroenterology, Hepatology and Nutrition Division, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104-4318, United States.

Abstract

Although the partitioning of apolipoprotein A-I (apoA-I) molecules in plasma between high-density lipoprotein (HDL)-bound and -unbound states is an integral part of HDL metabolism, the factors that control binding of apoA-I to HDL particles are poorly understood. To address this gap in knowledge, we investigated how the properties of the apoA-I tertiary structure domains and surface characteristics of spherical HDL particles influence apoA-I binding. The abilities of (14)C-labeled human and mouse apoA-I variants to associate with human HDL and lipid emulsion particles were determined using ultracentrifugation to separate free and bound protein. The binding of human apoA-I (243 amino acids) to HDL is largely mediated by its relatively hydrophobic C-terminal domain; the isolated N-terminal helix bundle domain (residues 1-190) binds poorly. Mouse apoA-I, which has a relatively polar C-terminal domain, binds to human HDL to approximately half the level of human apoA-I. The HDL binding abilities of apoA-I variants correlate strongly with their abilities to associate with phospholipid (PL)-stabilized emulsion particles, consistent with apoA-I-PL interactions at the particle surface being important. When equal amounts of HDL2 and HDL3 are present, all of the apoA-I variants partition preferentially to HDL3. Fluorescence polarization measurements using Laurdan-labeled HDL2 and HDL3 indicate that PL molecular packing is looser on the more negatively charged HDL3 particle surface, which promotes apoA-I binding. Overall, it is clear that both apoA-I structural features, especially the hydrophobicity of the C-terminal domain, and HDL surface characteristics such as the availability of free space influence the ability of apoA-I to associate with HDL particles.

PMID:
23425306
PMCID:
PMC3603221
DOI:
10.1021/bi400032y
[Indexed for MEDLINE]
Free PMC Article

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