title: Backbone and side-chain resonance assignment of the A147T polymorph of mouse TSPO in complex with a high-affinity radioligand.
abstract: The integral polytopic membrane protein TSPO is the target for numerous endogenous and synthetic ligands. However, the affinity of many ligands is influenced by a common polymorphism in TSPO, in which an alanine at position 147 is replaced by threonine, thereby complicating the use of several radioligands for clinical diagnosis. In contrast, the best-characterized TSPO ligand (R)-PK11195 binds with similar affinity to both variants of mitochondrial TSPO (wild-type and A147T variant). Here we report the (1)H, (13)C, (15)N backbone and side-chain resonance assignment of the A147T polymorph of TSPO from Mus Musculus in complex with (R)-PK11195 in DPC detergent micelles. More than 90 % of all resonances were sequence-specifically assigned, demonstrating the ability to obtain high-quality spectral data for both the backbone and the side-chains of medically relevant integral membrane proteins.
authors.affiliation: Max-Planck-Institut für Biophysikalische Chemie, 37077, Göttingen, Germany.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Jaremko
authors.affiliation: Max-Planck-Institut für Biophysikalische Chemie, 37077, Göttingen, Germany.|Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), 37077, Göttingen, Germany.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Jaremko
authors.affiliation: Max-Planck-Institut für Biophysikalische Chemie, 37077, Göttingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Giller
authors.affiliation: Max-Planck-Institut für Biophysikalische Chemie, 37077, Göttingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Becker
authors.affiliation: Max-Planck-Institut für Biophysikalische Chemie, 37077, Göttingen, Germany. Markus.Zweckstetter@dzne.de.|Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), 37077, Göttingen, Germany. Markus.Zweckstetter@dzne.de.|Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center, 37073, Göttingen, Germany. Markus.Zweckstetter@dzne.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
mesh_terms: D000818:Animals; D008024:Ligands; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017433:Protein Structure, Secondary; D019275:Radiopharmaceuticals / Q000378:metabolism*; D018079:Receptors, GABA / Q000737:chemistry* / Q000235:genetics*
chemical_list: C463819:Bzrp protein, mouse; D008024:Ligands; D019275:Radiopharmaceuticals; D018079:Receptors, GABA
keywords: (R)-PK11195; Membrane protein; NMR spectroscopy; Polymorphism; TSPO