High density lipoprotein structure-function and role in reverse cholesterol transport.
High density lipoprotein structure-function and role in reverse cholesterol transport.
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DOI：
10.1007/978-90-481-8622-8_7
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发表时间：
2010
影响因子：
--
通讯作者：
Phillips, Michael C.
中科院分区：
文献类型：
--
作者：
Lund-Katz, Sissel;Phillips, Michael C.
高密度脂蛋白（HDL）具有重要的抗动脉粥样硬化特性，本文综述了这些功能的分子机制。高密度脂蛋白颗粒的结构和胆固醇转运能力是由其可交换载脂蛋白（apo）成分的性质决定的。ApoA-I和apoE包含一系列的两亲性α-螺旋重复序列，在结构上表征最好。位于分子三分之二的氨基末端的螺旋采用螺旋束结构，而羧基末端部分形成单独折叠，相对无序的结构域。后一个结构域启动脂质结合，这种相互作用诱导构象的变化；α-螺旋含量增加，氨基端螺旋束随之打开。这些构象变化改变了apoA-I和apoE作为其受体配体的能力。apoA-I和apoE分子具有类似洗涤剂的性质，它们可以溶解囊状磷脂，形成盘状高密度脂蛋白颗粒，其水动力直径约为10 nm。在apoa - 1的例子中，这样的粒子是由两个蛋白质分子稳定的，它们排列在圆盘边缘的反平行双带构象中。apoA-I和apoE溶解磷脂和稳定HDL颗粒的能力使这些蛋白质与ABCA1成为伙伴，介导细胞磷脂和胆固醇的外排，以及HDL颗粒的生物生成。含apoa - i的新生HDL颗粒在循环中的胆固醇转运中起关键作用，而含apoe的HDL颗粒介导胆固醇在脑中的转运。本文综述了高密度脂蛋白颗粒被脂肪酶和脂质转移蛋白重塑，并与SR-BI相互作用将胆固醇传递到细胞的机制。
High density lipoprotein (HDL) possesses important anti-atherogenic properties and this review addresses the molecular mechanisms underlying these functions. The structures and cholesterol transport abilities of HDL particles are determined by the properties of their exchangeable apolipoprotein (apo) components. ApoA-I and apoE, which are the best characterized in structural terms, contain a series of amphipathic α-helical repeats. The helices located in the amino-terminal two-thirds of the molecule adopt a helix bundle structure while the carboxy-terminal segment forms a separately folded, relatively disorganized, domain. The latter domain initiates lipid binding and this interaction induces changes in conformation; the α-helix content increases and the amino-terminal helix bundle can open subsequently. These conformational changes alter the abilities of apoA-I and apoE to function as ligands for their receptors. The apoA-I and apoE molecules possess detergent-like properties and they can solubilize vesicular phospholipid to create discoidal HDL particles with hydrodynamic diameters of ~10 nm. In the case of apoA-I, such a particle is stabilized by two protein molecules arranged in an anti-parallel, double-belt, conformation around the edge of the disc. The abilities of apoA-I and apoE to solubilize phospholipid and stabilize HDL particles enable these proteins to be partners with ABCA1 in mediating efflux of cellular phospholipid and cholesterol, and the biogenesis of HDL particles. ApoA-I-containing nascent HDL particles play a critical role in cholesterol transport in the circulation whereas apoE-containing HDL particles mediate cholesterol transport in the brain. The mechanisms by which HDL particles are remodeled by lipases and lipid transfer proteins, and interact with SR-BI to deliver cholesterol to cells, are reviewed.
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影响因子：
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作者：
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DOI：
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DOI：
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发表时间：
2002-02-11
期刊：
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影响因子：
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作者：
Agree, AKB;Tricerri, MA;Jonas, A
通讯作者：
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