The 18-kilodalton translocator protein TSPO is found in mitochondrial membranes and mediates theimport of cholesterol and porphyrins into mitochondria. In line with the role of TSPO in mitochondrialfunction, TSPO ligands are used for a variety of diagnostic and therapeutic applications in animalsand humans. We present the three-dimensional high-resolution structure of mammalian TSPO reconstitutedin detergent micelles in complex with its high-affinity ligand PK11195. The TSPO-PK11195 structure isdescribed by a tight bundle of five transmembrane a helices that form a hydrophobic pocket acceptingPK11195. Ligand-induced stabilization of the structure of TSPO suggests a molecular mechanism forthe stimulation of cholesterol transport into mitochondria.
- Jaremko L, Jaremko M, Giller K, Becker S, Zweckstetter M.
Science. 2014 Mar 21;343(6177):1363-6.