TY  - JOUR
AU  - Zeng, Juan
AU  - Guareschi, Riccardo
AU  - Damre, Mangesh
AU  - Cao, Ruyin
AU  - Kless, Achim
AU  - Neumaier, Bernd
AU  - Bauer, Andreas
AU  - Giorgetti, Alejandro
AU  - Carloni, Paolo
AU  - Rossetti, Giulia
TI  - Structural Prediction of the Dimeric Form of the Mammalian Translocator Membrane Protein TSPO: A Key Target for Brain Diagnostics
JO  - International journal of molecular sciences
VL  - 19
IS  - 9
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - FZJ-2018-05717
SP  - 2588 -
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30200318
UR  - <Go to ISI:>//WOS:000449988100124
DO  - DOI:10.3390/ijms19092588
UR  - https://juser.fz-juelich.de/record/856050
ER  -