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Structural Integrity of the A147T Polymorph of Mammalian TSPO |
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| Authors: | Dr Mariusz Jaremko Dr ?ukasz Jaremko Karin Giller Dr Stefan Becker Prof Dr Markus Zweckstetter |
| Affiliation: | 1. Department for NMR‐Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 G?ttingen (Germany);2. German Center for Neurodegenerative Diseases (DZNE), 37077 G?ttingen (Germany);3. DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), University Medical Center G?ttingen, 37073 G?ttingen (Germany) |
| Abstract: | Ligands of the transmembrane protein TSPO are used for imaging of brain inflammation, but a common polymorphism in TSPO complicates their application to humans. Here we determined the three‐dimensional structure and side‐chain dynamics of the A147T polymorph of mammalian TSPO in complex with the first‐generation ligand PK11195. We show that A147T TSPO is able to retain the same structural and dynamic profile as the wild‐type protein and thus binds PK11195 with comparable affinity. Our study is important for the design of more potent diagnostic and therapeutic ligands of TSPO. |
| Keywords: | dynamics membrane proteins NMR spectroscopy polymorphism protein structures |