Structural Prediction of the Dimeric Form of the Mammalian Translocator Membrane Protein TSPO: A Key Target for Brain Diagnostics
| العنوان: | Structural Prediction of the Dimeric Form of the Mammalian Translocator Membrane Protein TSPO: A Key Target for Brain Diagnostics |
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| المؤلفون: | Alejandro Giorgetti, Bernd Neumaier, Ruyin Cao, Giulia Rossetti, Andreas Bauer, Mangesh V. Damre, Achim Kless, Riccardo Guareschi, Paolo Carloni, Juan Zeng |
| المصدر: | International Journal of Molecular Sciences International journal of molecular sciences 19(9), 2588-(2018). doi:10.3390/ijms19092588 Volume 19 Issue 9 International Journal of Molecular Sciences, Vol 19, Iss 9, p 2588 (2018) International journal of molecular sciences 19(9), 2588 (2018). doi:10.3390/ijms19092588 |
| بيانات النشر: | RWTH Aachen University, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Dimer, homology modeling, Mouse Protein, Ligands, 01 natural sciences, Catalysis, Article, oligomerization, lcsh:Chemistry, Inorganic Chemistry, 03 medical and health sciences, Molecular dynamics, chemistry.chemical_compound, Receptors, GABA, radioligands, 0103 physical sciences, Animals, Homology modeling, Physical and Theoretical Chemistry, lcsh:QH301-705.5, Molecular Biology, Spectroscopy, brain inflammation, Binding Sites, 010304 chemical physics, Chemistry, Organic Chemistry, General Medicine, Nmr data, molecular dynamics, Computer Science Applications, Molecular Docking Simulation, 030104 developmental biology, Membrane, PET, Cholesterol, lcsh:Biology (General), lcsh:QD1-999, Membrane protein, Docking (molecular), Positron-Emission Tomography, ddc:540, docking, Biophysics, TSPO, Protein Multimerization, Protein Binding |
| الوصف: | Positron emission tomography (PET) radioligands targeting the human translocator membrane protein (TSPO) are broadly used for the investigations of neuroinflammatory conditions associated with neurological disorders. Structural information on the mammalian protein homodimers&mdash the suggested functional state of the protein&mdash is limited to a solid-state nuclear magnetic resonance (NMR) study and to a model based on the previously-deposited solution NMR structure of the monomeric mouse protein. Computational studies performed here suggest that the NMR-solved structure in the presence of detergents is not prone to dimer formation and is furthermore unstable in its native membrane environment. We, therefore, propose a new model of the functionally-relevant dimeric form of the mouse protein, based on a prokaryotic homologue. The model, fully consistent with solid-state NMR data, is very different from the previous predictions. Hence, it provides, for the first time, structural insights into this pharmaceutically-important target which are fully consistent with experimental data. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.18154/rwth-conv-236158 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3d3f67d1b85100906830fce24d8cb64 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f3d3f67d1b85100906830fce24d8cb64 |
| قاعدة البيانات: | OpenAIRE |
| DOI: | 10.18154/rwth-conv-236158 |
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