Senior Research Group of Translational Structural Biology in Dementia, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Von-Siebold-Str. 3a, 37075, Göttingen, Germany.
Department of Neurology, University Medical Center Göttingen, University of Göttingen, Waldweg 33, 37073, Göttingen, Germany.
Eur Biophys J. 2021 Mar;50(2):173-180. doi: 10.1007/s00249-020-01487-0. Epub 2020 Dec 22.
Translocator Protein (18 kDa) (TSPO) is a mitochondrial transmembrane protein commonly used as a biomarker for neuroinflammation and is also a potential therapeutic target in neurodegenerative diseases. Despite intensive research efforts, the function of TSPO is still largely enigmatic. Deciphering TSPO structure in the native lipid environment is essential to gain insight into its cellular activities and to design improved diagnostic and therapeutic ligands. Here, we discuss the influence of lipid composition on the structure of mammalian TSPO embedded into lipid bilayers on the basis of solid-state NMR experiments. We further highlight that cholesterol can influence both the tertiary and quaternary TSPO structure and also influence TSPO localization in mitochondria-associated endoplasmic reticulum membranes.
转位蛋白（18kDa）（TSPO）是一种线粒体跨膜蛋白，通常用作神经炎症的生物标志物，也是神经退行性疾病的潜在治疗靶点。尽管进行了大量研究，但 TSPO 的功能仍然很大程度上是个谜。解析天然脂质环境中的 TSPO 结构对于深入了解其细胞活性以及设计改进的诊断和治疗配体至关重要。在这里，我们根据固态 NMR 实验讨论了脂质组成对嵌入脂质双层中的哺乳动物 TSPO 结构的影响。我们进一步强调胆固醇可以影响 TSPO 的三级和四级结构，并影响 TSPO 在与内质网相关的线粒体中的定位。
