Oxysterol-Binding Proteins
Oxysterol-Binding Proteins
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DOI：
10.1007/978-90-481-8622-8_6
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发表时间：
2010-01-01
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影响因子：
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通讯作者：
Ridgway, Neale D.
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作者：
Ridgway, Neale D.
在真核细胞中，与内质网、核膜和线粒体相关的晚期分泌途径的膜含有大量的胆固醇。在一个极端，富含胆固醇和鞘脂的质膜对于参与细胞通讯和运输的液体有序结构域（筏）的形成至关重要。另一方面，内质网中的调节机制维持在胆固醇相对贫乏的环境中，以确保对细胞固醇水平的波动做出适当的快速反应。因此，胆固醇稳态完全依赖于其沿着细胞内梯度的分布。很明显，这种梯度是由固醇-脂质相互作用、囊泡转运和固醇结合/转运蛋白的组合维持的。细胞器之间的快速，不依赖于能量的运输的证据已经牵连到运输蛋白，特别是真核氧化固醇结合蛋白（OSBP）家族。由于该家族的创始成员在超过25年前被确定，累积的证据表明OSBP和OSBP相关蛋白（ORP）的12个成员家族参与固醇信号传导和/或固醇转运功能。OSBP/ORP基因家族的特征在于保守的β-桶甾醇结合折叠，但通过靶向多个细胞器膜的额外结构域的存在而与其他甾醇结合蛋白质区分。在这里，我们将讨论哺乳动物OSBP/ORP家族的功能和结构特征，支持膜之间的固醇运输的“双靶向”模型。
In eukaryotic cells, membranes of the late secretory pathway contain a disproportionally large amount of cholesterol in relation to the endoplasmic reticulum, nuclear envelope and mitochondria. At one extreme, enrichment of the plasma membrane with cholesterol and sphingolipids is crucial for formation of liquid ordered domains (rafts) involved in cell communication and transport. On the other hand, regulatory machinery in the endoplasmic reticulum is maintained in a relatively cholesterol-poor environment, to ensure appropriate rapid responses to fluctuations in cellular sterol levels. Thus, cholesterol homeostasis is absolutely dependent on its distribution along an intracellular gradient. It is apparent that this gradient is maintained by a combination of sterol-lipid interactions, vesicular transport and sterol-binding/transport proteins. Evidence for rapid, energy-independent transport between organelles has implicated transport proteins, in particular the eukaryotic oxysterol binding protein (OSBP) family. Since the founding member of this family was identified more than 25 years ago, accumulated evidence implicates the 12-member family of OSBP and OSBP-related proteins (ORPs) in sterol signalling and/or sterol transport functions. The OSBP/ORP gene family is characterized by a conserved beta-barrel sterol-binding fold but is differentiated from other sterol-binding proteins by the presence of additional domains that target multiple organelle membranes. Here we will discuss the functional and structural characteristics of the mammalian OSBP/ORP family that support a 'dual-targeting' model for sterol transport between membranes.