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.
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August 2015
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Review Article|
August 03 2015
Structure of the mammalian TSPO/PBR protein
Mariusz Jaremko;
Mariusz Jaremko
1
*Max-Planck-Institut für Biophysikalische Chemie, Göttingen 37077, Germany
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Łukasz Jaremko;
Łukasz Jaremko
1
*Max-Planck-Institut für Biophysikalische Chemie, Göttingen 37077, Germany
†Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Göttingen 37077, Germany
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Garima Jaipuria;
Garima Jaipuria
*Max-Planck-Institut für Biophysikalische Chemie, Göttingen 37077, Germany
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Stefan Becker;
Stefan Becker
*Max-Planck-Institut für Biophysikalische Chemie, Göttingen 37077, Germany
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Markus Zweckstetter
Markus Zweckstetter
2
*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
2To whom correspondence should be addressed (emailMarkus.Zweckstetter@dzne.de).
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Biochem Soc Trans (2015) 43 (4): 566–571.
Article history
Received:
January 27 2015
Citation
Mariusz Jaremko, Łukasz Jaremko, Garima Jaipuria, Stefan Becker, Markus Zweckstetter; Structure of the mammalian TSPO/PBR protein. Biochem Soc Trans 1 August 2015; 43 (4): 566–571. doi: https://doi.org/10.1042/BST20150029
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