Protein structure. Structure and activity of tryptophan-rich TSPO proteins

Science. 2015 Jan 30;347(6221):551-5. doi: 10.1126/science.aaa1534.


Translocator proteins (TSPOs) bind steroids and porphyrins, and they are implicated in many human diseases, for which they serve as biomarkers and therapeutic targets. TSPOs have tryptophan-rich sequences that are highly conserved from bacteria to mammals. Here we report crystal structures for Bacillus cereus TSPO (BcTSPO) down to 1.7 Å resolution, including a complex with the benzodiazepine-like inhibitor PK11195. We also describe BcTSPO-mediated protoporphyrin IX (PpIX) reactions, including catalytic degradation to a previously undescribed heme derivative. We used structure-inspired mutations to investigate reaction mechanisms, and we showed that TSPOs from Xenopus and man have similar PpIX-directed activities. Although TSPOs have been regarded as transporters, the catalytic activity in PpIX degradation suggests physiological importance for TSPOs in protection against oxidative stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacillus cereus / chemistry*
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Crystallography, X-Ray
  • Isoquinolines / metabolism
  • Ligands
  • Membrane Transport Proteins / chemistry*
  • Membrane Transport Proteins / metabolism*
  • Molecular Sequence Data
  • Mutant Proteins / chemistry
  • Mutant Proteins / metabolism
  • Protein Conformation
  • Protein Multimerization
  • Protein Structure, Secondary
  • Protein Subunits / chemistry
  • Protoporphyrins / metabolism
  • Reactive Oxygen Species / metabolism
  • Tryptophan / analysis


  • Bacterial Proteins
  • Isoquinolines
  • Ligands
  • Membrane Transport Proteins
  • Mutant Proteins
  • Protein Subunits
  • Protoporphyrins
  • Reactive Oxygen Species
  • Tryptophan
  • protoporphyrin IX
  • PK 11195