title: Structure of the mammalian TSPO/PBR protein.
abstract: The 3D structure of the 18-kDa transmembrane (TM) protein TSPO (translocator protein)/PBR (peripheral benzodiazepine receptor), which contains a binding site for benzodiazepines, is important to better understand its function and regulation by endogenous and synthetic ligands. We have recently determined the structure of mammalian TSPO/PBR in complex with the diagnostic ligand PK11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; Jaremko et al. (2014) Science 343: , 1363-1366], providing for the first time atomic-level insight into the conformation of this protein, which is up-regulated in various pathological conditions including Alzheimer's disease and Parkinson's disease. Here, we review the studies which have probed the structural properties of mammalian TSPO/PBR as well as the homologues bacterial tryptophan-rich sensory proteins (TspOs) over the years and provide detailed insight into the 3D structure of mouse TSPO (mTSPO)/PBR in complex with PK11195.
authors.affiliation: Max-Planck-Institut für Biophysikalische Chemie, Göttingen 37077, Germany.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Jaremko
authors.affiliation: Max-Planck-Institut für Biophysikalische Chemie, Göttingen 37077, Germany Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Göttingen 37077, Germany.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Jaremko
authors.affiliation: Max-Planck-Institut für Biophysikalische Chemie, Göttingen 37077, Germany.
authors.forename: Garima
authors.initials: G
authors.lastname: Jaipuria
authors.affiliation: Max-Planck-Institut für Biophysikalische Chemie, Göttingen 37077, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Becker
authors.affiliation: Max-Planck-Institut für Biophysikalische Chemie, Göttingen 37077, Germany Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Göttingen 37077, Germany Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center, Göttingen 37077, Germany Markus.Zweckstetter@dzne.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008322:Mammals / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D018079:Receptors, GABA / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C463819:Bzrp protein, mouse; D007546:Isoquinolines; D018079:Receptors, GABA; C037850:PK 11195
keywords: 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK11195); TSPO; dynamics; nuclear magnetic resonance (NMR); peripheral benzodiazepine receptor; structure