Structure of the Mitochondrial Translocator Protein in Complex with a Diagnostic Ligand

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Science  21 Mar 2014:
Vol. 343, Issue 6177, pp. 1363-1366
DOI: 10.1126/science.1248725

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Translocation in Injury

The translocator protein TSPO is essential for the import of cholesterol and porphyrins into mitochondria. TSPO expression increases in areas of brain injury and during neuroinflammation and, thus, has diagnostic and therapeutic implications. Jaremko et al. (p. 1363) used nuclear magnetic resonance spectroscopy to determine the high-resolution structure of the 18- kilodalton mammalian TSPO with the ligand PK11195, which stabilized the structure and resolved the conformation as a tight bundle of five helices.


The 18-kilodalton translocator protein TSPO is found in mitochondrial membranes and mediates the import of cholesterol and porphyrins into mitochondria. In line with the role of TSPO in mitochondrial function, TSPO ligands are used for a variety of diagnostic and therapeutic applications in animals and humans. We present the three-dimensional high-resolution structure of mammalian TSPO reconstituted in detergent micelles in complex with its high-affinity ligand PK11195. The TSPO-PK11195 structure is described by a tight bundle of five transmembrane α helices that form a hydrophobic pocket accepting PK11195. Ligand-induced stabilization of the structure of TSPO suggests a molecular mechanism for the stimulation of cholesterol transport into mitochondria.

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