دورية أكاديمية
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: | Juan Zeng, Riccardo Guareschi, Mangesh Damre, Ruyin Cao, Achim Kless, Bernd Neumaier, Andreas Bauer, Alejandro Giorgetti, Paolo Carloni, Giulia Rossetti |
| المصدر: | International Journal of Molecular Sciences, Vol 19, Iss 9, p 2588 (2018) |
| بيانات النشر: | MDPI AG, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | TSPO, radioligands, PET, oligomerization, brain inflammation, homology modeling, molecular dynamics, docking, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| 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—the suggested functional state of the protein—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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 |
| Relation: | http://www.mdpi.com/1422-0067/19/9/2588; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms19092588 |
| URL الوصول: | https://doaj.org/article/519dbc030bd54fe880cb7de79f314a95 |
| رقم الأكسشن: | edsdoj.519dbc030bd54fe880cb7de79f314a95 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 |
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| DOI: | 10.3390/ijms19092588 |