2mgy
Solution structure of the mitochondrial translocator protein (TSPO) in complex with its high-affinity ligand PK11195
Structural highlights
FunctionTSPO_MOUSE Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides. Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:9832438, PubMed:24814875), but its precise physiological role is controversial. According to some reports, it is not required for steroid hormone biosynthesis (PubMed:24174323, PubMed:24936060).[1] [2] [3] [4] [5] Publication Abstract from PubMedThe 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 alpha 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. Structure of the mitochondrial translocator protein in complex with a diagnostic ligand.,Jaremko L, Jaremko M, Giller K, Becker S, Zweckstetter M Science. 2014 Mar 21;343(6177):1363-6. doi: 10.1126/science.1248725. PMID:24653034[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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