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Backbone and side-chain resonance assignment of the A147T polymorph of mouse TSPO in complex with a high-affinity radioligand

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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 1H, 13C, 15N 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.

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Acknowledgments

1H, 13C, 15N resonance assignments of the A147T-mTSPO/PK11195 complex have been deposited at the BMRB data base (Accession Code: 25513). This work was partially supported by the DFG Collaborative Research Center 803, Project A11.

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    Authors and Affiliations

    1. Max-Planck-Institut für Biophysikalische Chemie, 37077, Göttingen, Germany

      Mariusz Jaremko, Łukasz Jaremko, Karin Giller, Stefan Becker & Markus Zweckstetter

    2. Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), 37077, Göttingen, Germany

      Łukasz Jaremko & Markus Zweckstetter

    3. Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center, 37073, Göttingen, Germany

      Markus Zweckstetter

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    1. Mariusz Jaremko
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    Correspondence to Markus Zweckstetter.

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    Mariusz Jaremko and Łukasz Jaremko have contributed equally to this work.

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    Jaremko, M., Jaremko, Ł., Giller, K. et al. Backbone and side-chain resonance assignment of the A147T polymorph of mouse TSPO in complex with a high-affinity radioligand. Biomol NMR Assign 10, 79–83 (2016). https://doi.org/10.1007/s12104-015-9642-y

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