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Conformational Flexibility in the Transmembrane Protein TSPO
Author(s) -
Jaremko Łukasz,
Jaremko Mariusz,
Giller Karin,
Becker Stefan,
Zweckstetter Markus
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201502314
Subject(s) - translocator protein , chemistry , biophysics , transmembrane protein , nuclear magnetic resonance spectroscopy , ligand (biochemistry) , integral membrane protein , radioligand , protein structure , transmembrane domain , membrane , crystallography , membrane protein , binding site , stereochemistry , biochemistry , receptor , biology , neuroinflammation , immunology , inflammation
The translocator protein (TSPO) is an integral membrane protein that interacts with a wide variety of endogenous ligands, such as cholesterol and porphyrins, and is also the target for several small molecules with substantial in vivo efficacy. When complexed with the TSPO‐specific radioligand ( R )‐PK11195, TSPO folds into a rigid five‐helix bundle. However, little is known about the structure and dynamics of TSPO in the absence of high‐affinity ligands. By means of NMR spectroscopy, we show that TSPO exchanges between multiple conformations in the absence of ( R )‐PK11195. Extensive motions on time scales from pico‐ to microseconds occur all along the primary sequence of the protein, leading to a loss of stable tertiary interactions and local unfolding of the helical structure in the vicinity of the ligand‐binding site. The flexible nature of TSPO highlights the importance of conformational plasticity in integral membrane proteins.