脂质转运蛋白：脂质通过穿梭车、桥梁和管道运输。,Nature Reviews Molecular Cell Biology

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脂质转运蛋白：脂质通过穿梭车、桥梁和管道运输。
Nature Reviews Molecular Cell Biology ( IF 81.3 ) Pub Date : 2019-02-01 , DOI: 10.1038/s41580-018-0071-5
Louise H Wong ₁ , Alberto T Gatta _{2,

3} , Tim P Levine ₁

Affiliation

脂质以高度异质的方式分布在不同的细胞膜中。只有少数脂质通过囊泡运输实现其最终的细胞内分布。相反，大部分脂质运输是由一大群脂质转运蛋白 (LTP) 介导的，它们使用稳定膜外脂质分子的疏水腔一次移动少量脂质。尽管第一个 LTP 是在近 50 年前发现的，但在过去几年中在理解这些蛋白质方面取得了大部分进展，导致我们对这些脂质转运蛋白功能的理解在时间和空间上进行了相当大的改进。已知 LTP 的数量已经增加，其多聚体组装的发现令人兴奋。LTP 的结构研究已经从静态晶体结构发展到动态结构方法，这些方法显示了构象变化如何在亚毫秒时间尺度上促进脂质处理。一项重大进展是发现许多细胞内 LTP 同时定位于两个细胞器，形成连接供体和受体隔室的穿梭、桥或管。了解不同脂质如何在分子水平上达到其最终目的地，可以更好地解释与脂质运输和分布相关的疾病中发生的缺陷范围，从而为开发专门针对脂质转移的疗法开辟了可能性。一项重大进展是发现许多细胞内 LTP 同时定位于两个细胞器，形成连接供体和受体隔室的穿梭、桥或管。了解不同脂质如何在分子水平上达到其最终目的地，可以更好地解释与脂质运输和分布相关的疾病中发生的缺陷范围，从而为开发专门针对脂质转移的疗法开辟了可能性。一项重大进展是发现许多细胞内 LTP 同时定位于两个细胞器，形成连接供体和受体隔室的穿梭、桥或管。了解不同脂质如何在分子水平上达到其最终目的地，可以更好地解释与脂质运输和分布相关的疾病中发生的缺陷范围，从而为开发专门针对脂质转移的疗法开辟了可能性。

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Lipid transfer proteins: the lipid commute via shuttles, bridges and tubes.

Lipids are distributed in a highly heterogeneous fashion in different cellular membranes. Only a minority of lipids achieve their final intracellular distribution through transport by vesicles. Instead, the bulk of lipid traffic is mediated by a large group of lipid transfer proteins (LTPs), which move small numbers of lipids at a time using hydrophobic cavities that stabilize lipid molecules outside membranes. Although the first LTPs were discovered almost 50 years ago, most progress in understanding these proteins has been made in the past few years, leading to considerable temporal and spatial refinement of our understanding of the function of these lipid transporters. The number of known LTPs has increased, with exciting discoveries of their multimeric assembly. Structural studies of LTPs have progressed from static crystal structures to dynamic structural approaches that show how conformational changes contribute to lipid handling at a sub-millisecond timescale. A major development has been the finding that many intracellular LTPs localize to two organelles at the same time, forming a shuttle, bridge or tube that links donor and acceptor compartments. The understanding of how different lipids achieve their final destination at the molecular level allows a better explanation of the range of defects that occur in diseases associated with lipid transport and distribution, opening up the possibility of developing therapies that specifically target lipid transfer.

更新日期：2019-01-26

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