Structure of sterol carrier protein 2 at 1.8 Å resolution reveals a hydrophobic tunnel suitable for lipid binding
Structure of sterol carrier protein 2 at 1.8 Å resolution reveals a hydrophobic tunnel suitable for lipid binding
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DOI：
10.1021/bi992742e
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发表时间：
2000-02-29
期刊：
影响因子：
2.9
通讯作者：
Piontek, K
中科院分区：
文献类型：
--
作者：
Choinowski, T;Hauser, H;Piontek, K
甾醇载体蛋白2，又称非特异性脂质转移蛋白，是一种普遍存在于动物体内的小分子基础蛋白，分子量为13kda。它的初级结构在不同物种之间高度保守，并与脂质的细胞内运输以及与固醇和脂肪酸代谢有关的广泛的其他体外功能有关。小鼠体内固醇载体蛋白2缺乏可导致血清中植酸浓度升高，从而导致肝癌的发生。然而，其实际的生理作用尚不清楚。在过去的20年里，人们对甾醇载体蛋白2进行了广泛的研究，但对其三维结构知之甚少。用MIRAS方法在1.8埃分辨率下测定了兔甾醇载体蛋白2的晶体结构，显示出独特的α / β折叠。这种蛋白质的核心形成了一个五股反平行的β -片，两侧有五个螺旋。c端片段（残基114-123）与部分β -sheet和四个α -螺旋一起形成疏水通道，为极性配体（如脂肪酸和脂肪酰基辅酶as）提供环境。结构表征良好的植物非特异性脂转移蛋白具有疏水隧道样空腔，这些空腔被确定为脂肪酸和相关极性配体的结合位点。尽管植物非特异性脂质转移蛋白比甾醇载体蛋白2更小，与甾醇载体蛋白2没有序列同源性，并且在结构上不相关，但这两类蛋白的空腔在大小、形状和疏水性方面非常相似，表明它们具有共同的功能作用。
Sterol carrier protein 2, also known as nonspecific lipid transfer protein is a ubiquitous, small, basic protein of 13 kDa found in animals. Its primary structure is highly conserved between different species, and it has been implicated in the intracellular transport of lipids and in a wide range of other in vitro functions related to sterol and fatty acid metabolism. Sterol carrier protein 2 deficiency in mice leads to elevated concentrations of phytanic acid in the serum and causes hepatocarcinogenesis. However, its actual physiological role is still unknown. Although sterol carrier protein 2 has been studied extensively in the past 20 years, very little is known concerning its three-dimensional structure. The crystal structure of rabbit sterol carrier protein 2, determined at 1.8 Angstrom resolution with the MIRAS method, shows a unique alpha/beta-fold. The core of this protein forms a five-stranded antiparallel beta-sheet flanked by five helices. A C-terminal segment (residues 114-123), together with part of the beta-sheet and four alpha-helices, form a hydrophobic tunnel providing the environment for apolar ligands such as fatty acids and fatty acyl-coenzyme As. Structurally well-characterized nonspecific lipid transfer proteins from plants have hydrophobic tunnel-like cavities, which were identified as the binding site for fatty acids and related apolar ligands. Despite the fact that plant nonspecific lipid transfer proteins are smaller proteins than sterol carrier protein 2, show no sequence homology to sterol carier protein 2, and are structurally unrelated, the cavities of these two classes of proteins are very similar with respect to size, shape, and hydrophobicity, suggesting a common functional role.