title: Structure of the mitochondrial translocator protein in complex with a diagnostic ligand.
abstract: 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.
authors.affiliation: Max-Planck-Institut für Biophysikalische Chemie, 37077 Göttingen, Germany.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Jaremko
authors.forename: Mariusz
authors.initials: M
authors.lastname: Jaremko
authors.forename: Karin
authors.initials: K
authors.lastname: Giller
authors.forename: Stefan
authors.initials: S
authors.lastname: Becker
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D007546:Isoquinolines / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008823:Micelles; D008928:Mitochondria / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D018079:Receptors, GABA / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: C463819:Bzrp protein, mouse; D007546:Isoquinolines; D008024:Ligands; D008823:Micelles; D033681:Mitochondrial Membrane Transport Proteins; D018079:Receptors, GABA; D011994:Recombinant Proteins; D002784:Cholesterol; C037850:PK 11195