Description: Structural Prediction of the Dimeric Form of the Mammalian Translocator Membrane Protein TSPO: A Key Target for Brain Diagnostics

This title appears in the Scientific Report : 2018

Structural Prediction of the Dimeric Form of the Mammalian Translocator Membrane Protein TSPO: A Key Target for Brain Diagnostics

Positron emission tomography (PET) radioligands targeting the human translocatormembrane protein (TSPO) are broadly used for the investigations of neuroinflammatory conditionsassociated with neurological disorders. Structural information on the mammalian proteinhomodimers—the suggested functional st...

Personal Name(s):	Zeng, Juan
	Guareschi, Riccardo / Damre, Mangesh / Cao, Ruyin / Kless, Achim / Neumaier, Bernd / Bauer, Andreas / Giorgetti, Alejandro / Carloni, Paolo / Rossetti, Giulia (Corresponding author)
Contributing Institute:	Jülich Supercomputing Center; JSC Computational Biomedicine; IAS-5 Molekulare Organisation des Gehirns; INM-2 Nuklearchemie; INM-5 Computational Biomedicine; INM-9
Published in:	International journal of molecular sciences, 19 (2018) 9, S. 2588 -
Imprint:	Basel Molecular Diversity Preservation International 2018
DOI:	10.3390/ijms19092588
PubMed ID:	30200318
Document Type:	Journal Article
Research Program:	Computational Science and Mathematical Methods Connectivity and Activity Condensed Matter and Molecular Building Blocks Neuroimaging
Link:	OpenAccess OpenAccess
	Publikationsportal JuSER

Please use the identifier: http://hdl.handle.net/2128/19793 in citations.
Please use the identifier: http://dx.doi.org/10.3390/ijms19092588 in citations.

Positron emission tomography (PET) radioligands targeting the human translocatormembrane protein (TSPO) are broadly used for the investigations of neuroinflammatory conditionsassociated with neurological disorders. Structural information on the mammalian proteinhomodimers—the suggested functional state of the protein—is limited to a solid-state nuclearmagnetic resonance (NMR) study and to a model based on the previously-deposited solution NMRstructure of the monomeric mouse protein. Computational studies performed here suggest thatthe NMR-solved structure in the presence of detergents is not prone to dimer formation and isfurthermore unstable in its native membrane environment. We, therefore, propose a new modelof 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 targetwhich are fully consistent with experimental data.