Conformational Flexibility in the Transmembrane Protein TSPO

Łukasz Jaremko, Mariusz Jaremko, Karin Giller, Stefan Becker, Markus Zweckstetter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)16555-16563
Number of pages9
JournalChemistry - A European Journal
Issue number46
StatePublished - Nov 1 2015
Externally publishedYes


  • NMR spectroscopy
  • dynamics
  • function
  • membrane proteins
  • small molecules
  • structure

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry


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