Translocator Protein 18 kDa (TSPO): An Old Protein with New Functions?
Translocator Protein 18 kDa (TSPO): An Old Protein with New Functions?
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DOI：
10.1021/acs.biochem.6b00142
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发表时间：
2016-05-24
期刊：
影响因子：
2.9
通讯作者：
Ferguson-Millert, Shelagh
中科院分区：
文献类型：
--
作者：
Li, Fei;Liu, Jian;Liu, Nan;Kuhn, Leslie A.;Garavito, R. Michael;Ferguson-Millert, Shelagh
易位蛋白 18 kDa (TSPO) 以前被称为真核生物中的外周苯二氮卓受体 (PBR)，主要定位于线粒体外膜。大量证据表明，它在类固醇生成和细胞凋亡中发挥调节作用，并与多种人类疾病有关，如转移性癌症、阿尔茨海默病和帕金森病、炎症和焦虑症。尽管对 TSPO 的功能尚无明确了解，但 TSPO 配体被广泛用作诊断工具和治疗选择。独立发现了光合细菌红细菌中的直系同源物，即富含色氨酸的感觉蛋白（TspO），并发现它在调节光合作用和呼吸的氧气和光照条件变化的反应中发挥作用。作为在所有三个王国中发现的高度保守的蛋白质家族的一部分，大鼠 TSPO 能够挽救红杆菌中的敲除表型，表明功能和结构的保守性。最近，该领域取得了重大突破：几个独立小组确定了不同物种的 TSPO 的原子分辨率结构。现在，我们可以从分子角度重新审视 TSPO 的功能。在这篇综述中，我们重点关注最近确定的 TSPO 结构及其对这种普遍存在的多面蛋白潜在功能的影响。我们认为 TSPO 是一种古老的细菌受体/应激传感器，在真核生物的线粒体外膜环境中已经发展出额外的相互作用、伙伴和作用。
Translocator protein 18 kDa (TSPO) was previously known as the peripheral benzodiazepine receptor (PBR) in eukaryotes, where it is mainly localized to the mitochondrial outer membrane. Considerable evidence indicates that it plays regulatory roles in steroidogenesis and apoptosis and is involved in various human diseases, such as metastatic cancer, Alzheimer’s and Parkinson’s disease, inflammation, and anxiety disorders. Ligands of TSPO are widely used as diagnostic tools and treatment options, despite there being no clear understanding of the function of TSPO. An ortholog in the photosynthetic bacterium Rhodobacter was independently discovered as the tryptophan-rich sensory protein (TspO) and found to play a role in the response to changes in oxygen and light conditions that regulate photosynthesis and respiration. As part of this highly conserved protein family found in all three kingdoms, the rat TSPO is able to rescue the knockout phenotype in Rhodobacter, indicating functional as well as structural conservation. Recently, a major breakthrough in the field was achieved: the determination of atomic-resolution structures of TSPO from different species by several independent groups. This now allows us to reexamine the function of TSPO with a molecular perspective. In this review, we focus on recently determined structures of TSPO and their implications for potential functions of this ubiquitous multifaceted protein. We suggest that TSPO is an ancient bacterial receptor/stress sensor that has developed additional interactions, partners, and roles in its mitochondrial outer membrane environment in eukaryotes.
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影响因子：
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作者：
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影响因子：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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