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@ARTICLE{Zeng:856050,
author = {Zeng, Juan and Guareschi, Riccardo and Damre, Mangesh and
Cao, Ruyin and Kless, Achim and Neumaier, Bernd and Bauer,
Andreas and Giorgetti, Alejandro and Carloni, Paolo and
Rossetti, Giulia},
title = {{S}tructural {P}rediction of the {D}imeric {F}orm of the
{M}ammalian {T}ranslocator {M}embrane {P}rotein {TSPO}: {A}
{K}ey {T}arget for {B}rain {D}iagnostics},
journal = {International journal of molecular sciences},
volume = {19},
number = {9},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {FZJ-2018-05717},
pages = {2588 -},
year = {2018},
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.},
cin = {INM-9 / INM-5 / INM-2 / IAS-5 / JSC},
ddc = {540},
cid = {I:(DE-Juel1)INM-9-20140121 / I:(DE-Juel1)INM-5-20090406 /
I:(DE-Juel1)INM-2-20090406 / I:(DE-Juel1)IAS-5-20120330 /
I:(DE-Juel1)JSC-20090406},
pnm = {573 - Neuroimaging (POF3-573) / 531 - Condensed Matter and
Molecular Building Blocks (POF3-531) / 571 - Connectivity
and Activity (POF3-571) / 511 - Computational Science and
Mathematical Methods (POF3-511)},
pid = {G:(DE-HGF)POF3-573 / G:(DE-HGF)POF3-531 /
G:(DE-HGF)POF3-571 / G:(DE-HGF)POF3-511},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30200318},
UT = {WOS:000449988100124},
doi = {10.3390/ijms19092588},
url = {https://juser.fz-juelich.de/record/856050},
}