Interactions of Apolipoprotein A-I with High-Density Lipoprotein Particles

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• 作者：David Nguyen ; Margaret Nickel ; Chiharu Mizuguchi ; Hiroyuki Saito ; Sissel Lund-Katz ; Michael C. Phillips
• 刊名：Biochemistry
• 出版年：2013
• 出版时间：March 19, 2013
• 年：2013
• 卷：52
• 期：11
• 页码：1963-1972
• 全文大小：443K
• 年卷期：v.52,no.11(March 19, 2013)
• ISSN：1520-4995

文摘

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 ¹⁴C-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鈥?90) 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鈥揚L 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.