Conformational Flexibility in the Transmembrane Protein TSPO
2015 | journal article. A publication with affiliation to the University of Göttingen.
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Conformational Flexibility in the Transmembrane Protein TSPO
Jaremko, L.; Jaremko, M.; Giller, K.; Becker, S. & Zweckstetter, M. (2015)
Chemistry - A European Journal, 21(46) pp. 16555-16563. DOI: https://doi.org/10.1002/chem.201502314
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- Authors
- Jaremko, Lukasz; Jaremko, Mariusz; Giller, Karin; Becker, Stefan; Zweckstetter, Markus
- Abstract
- 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.
- Issue Date
- 2015
- Status
- published
- Publisher
- Wiley-v C H Verlag Gmbh
- Journal
- Chemistry - A European Journal
- ISSN
- 1521-3765; 0947-6539