The structure of dimeric apolipoprotein A-IV and its mechanism of self-association.

The structure of dimeric apolipoprotein A-IV and its mechanism of self-association.
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DOI:
10.1016/j.str.2012.02.020
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发表时间:
2012-05-09
期刊:
影响因子:
5.7
通讯作者:
Thompson, Thomas B.
Thompson, Thomas B.
中科院分区:
生物学2区
文献类型:
--
作者:
Deng, Xiaodi;Morris, Jamie;Dressmen, James;Tubb, Matthew R.;Tso, Patrick;Jerome, W. Gray;Davidson, W. Sean;Thompson, Thomas B.

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载脂蛋白是脂蛋白的关键结构元素,也是脂代谢的关键介质。其类似洗涤剂的性质允许它们乳化脂肪或以可溶的无脂形式存在于不同的自结合状态。不幸的是,这些特征阻碍了理解心脏保护性高密度脂蛋白(HDL)的生物发生所需的高分辨率结构研究。我们推导了人载脂蛋白(Apo)A-IV核心区的晶体结构,apo A-IV是一种高密度脂蛋白成分,也是脂类吸收的重要介体。2.4ä的结构描绘了两个线性连接的4-螺旋束参与螺旋交换排列,这为蛋白质如何自结合以及其单体形式的结构提供了清晰的解释。这也为最近描述的含脂颗粒的反平行排列提供了逻辑基础。此外,我们还提出了载脂蛋白A-IV脂结合的“旋转门”模型。
Apolipoproteins are key structural elements of lipoproteins and critical mediators of lipid metabolism. Their detergent-like properties allow them to emulsify lipid or exist in a soluble lipid-free form in various states of self-association. Unfortunately, these traits have hampered high-resolution structural studies needed to understand the biogenesis of cardioprotective high-density lipoproteins (HDL). We derived a crystal structure of the core domain of human apolipoprotein (apo)A-IV, an HDL component and important mediator of lipid absorption. The structure at 2.4 Å depicts two linearly connected 4-helix bundles participating in a helix swapping arrangement that offers a clear explanation for how the protein self-associates as well as clues to the structure of its monomeric form. This also provides a logical basis for antiparallel arrangements recently described for lipid-containing particles. Furthermore, we propose a “swinging door” model for apoA-IV lipid association.
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