Journal Article

FZJ-2018-05717

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Structural Prediction of the Dimeric Form of the Mammalian Translocator Membrane Protein TSPO: A Key Target for Brain Diagnostics

Zeng, J.FZJ* ; Guareschi, R.FZJ* ; Damre, M. ; Cao, R. ; Kless, A. ; Neumaier, B.FZJ* ; Bauer, A.FZJ* ; Giorgetti, A.FZJ* ; Carloni, P.FZJ* ; Rossetti, G. (Corresponding author)FZJ*

2018
Molecular Diversity Preservation International Basel

This record in other databases:      

Please use a persistent id in citations: http://hdl.handle.net/2128/19793  doi:10.3390/ijms19092588

Abstract: 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.

---

Contributing Institute(s):

1. Computational Biomedicine (INM-9)
2. Nuklearchemie (INM-5)
3. Molekulare Organisation des Gehirns (INM-2)
4. Computational Biomedicine (IAS-5)
5. Jülich Supercomputing Center (JSC)

Research Program(s):

1. 573 - Neuroimaging (POF3-573) (POF3-573)
2. 531 - Condensed Matter and Molecular Building Blocks (POF3-531) (POF3-531)
3. 571 - Connectivity and Activity (POF3-571) (POF3-571)
4. 511 - Computational Science and Mathematical Methods (POF3-511) (POF3-511)

Appears in the scientific report 2018

---

Database coverage:
; ; ; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---