Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 21, Issue 46, Pages 16555-16563Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201502314
Keywords
dynamics; function; membrane proteins; NMR spectroscopy; small molecules; structure
Categories
Funding
- DFG Collaborative Research Center 803
- European Research Council [282008]
- European Research Council (ERC) [282008] Funding Source: European Research Council (ERC)
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available