Insights into the Molecular Mechanisms of Cholesterol Binding to the NPC1 and NPC2 Proteins
Insights into the Molecular Mechanisms of Cholesterol Binding to the NPC1 and NPC2 Proteins
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DOI：
10.1007/978-3-030-14265-0_8
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Rosenhouse-Dantsker, Avia
中科院分区：
文献类型：
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作者：
Cologna, Stephanie M.;Rosenhouse-Dantsker, Avia
近年来，越来越多的研究表明NPC1和NPC2在溶酶体内转运和胆固醇外流中的协调作用。我们目前对这一过程的理解是通过二十多年的研究而发展起来的。自从编码NPC1和NPC2蛋白的基因被克隆以来，对这两个基因突变时观察到的生化缺陷的研究以及计算和结构研究已经揭开了潜在机制中的关键步骤。在这里，我们总结了我们对NPC1和NPC2控制的胆固醇运输的主要贡献，并简要讨论了NPC1和NPC2以外的胆固醇结合和运输蛋白的最新发现。最后，我们总结了NPC1和NPC2蛋白在未来胆固醇转运研究中面临的关键问题和主要挑战。
In recent years, a growing number of studies have implicated the coordinated action of NPC1 and NPC2 in intralysosomal transport and efflux of cholesterol. Our current understanding of this process developed with just over two decades of research. Since the cloning of the genes encoding the NPC1 and NPC2 proteins, studies of the biochemical defects observed when either gene is mutated along with computational and structural studies have unraveled key steps in the underlying mechanism. Here, we summarize the major contributions to our understanding of the proposed cholesterol transport controlled by NPC1 and NPC2, and briefly discuss recent findings of cholesterol binding and transport proteins beyond NPC1 and NPC2. We conclude with key questions and major challenges for future research on cholesterol transport by the NPC1 and NPC2 proteins.