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@ARTICLE{Combet:917018,
author = {Combet, Sophie and Bonneté, Françoise and Finet,
Stéphanie and Pozza, Alexandre and Saade, Christelle and
Martel, Anne and Koutsioumpas, Alexandros and Lacapère,
Jean-Jacques},
title = {{E}ffect of amphiphilic environment on the solution
structure of mouse {TSPO} translocator protein},
journal = {Biochimie},
volume = {205},
issn = {0300-9084},
address = {Paris [u.a.]},
publisher = {Elsevier},
reportid = {FZJ-2023-00284},
pages = {61-72},
year = {2023},
abstract = {The translocator protein (TSPO) is a ubiquitous
transmembrane protein of great pharmacological interest
thanks to its high affinity to many drug ligands. The only
high-resolution 3D-structure known for mammalian TSPO was
obtained by NMR for the mouse mTSPO in DPC detergent only in
presence of the high-affinity PK 11195 ligand. An atomic
structure of free-ligand mTSPO is still missing to better
understand the interaction of ligands with mTSPO and their
effects on the protein conformation.Here, we decipher the
solution structures of the recombinant mTSPO without ligand
both in (i) SDS, the detergent used to extract and purify
the protein from E. coli inclusion bodies, and (ii) DPC, the
detergent used to solve the PK 11195-binding mTSPO NMR
structure.We report partially refolded and less flexible
mTSPO helices in DPC compared to SDS. Besides, DPC
stabilizes the tertiary structure of mTSPO, as shown by a
higher intrinsic Trp fluorescence and changes in indole
environment.We evaluate by SEC-MALLS that ∼135 SDS and
∼100 DPC molecules are bound to mTSPO. SEC-small-angle
X-ray (SAXS) and neutron (SANS) scattering confirm a larger
mTSPO-detergent complex in SDS than in DPC. Using the
contrast-matching technique in SEC-SANS, we demonstrate that
mTSPO conformation is more compact and less flexible in DPC
than in SDS. Combining ab initio modeling with SANS, we
confirm that mTSPO conformation is less elongated in DPC
than in SDS. However, the free-ligand mTSPO envelope in DPC
is not as compact as the PK 11195-binding protein NMR
structure, the ligand stiffening the protein.},
cin = {JCNS-FRM-II / MLZ / JCNS-1 / JCNS-4},
ddc = {540},
cid = {I:(DE-Juel1)JCNS-FRM-II-20110218 / I:(DE-588b)4597118-3 /
I:(DE-Juel1)JCNS-1-20110106 / I:(DE-Juel1)JCNS-4-20201012},
pnm = {6G4 - Jülich Centre for Neutron Research (JCNS) (FZJ)
(POF4-6G4) / 632 - Materials – Quantum, Complex and
Functional Materials (POF4-632)},
pid = {G:(DE-HGF)POF4-6G4 / G:(DE-HGF)POF4-632},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {36460205},
UT = {WOS:000943144700001},
doi = {10.1016/j.biochi.2022.11.014},
url = {https://juser.fz-juelich.de/record/917018},
}