4uc2

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Crystal structure of translocator protein 18kDa (TSPO) from rhodobacter sphaeroides (A139T mutant) in P212121 space groupCrystal structure of translocator protein 18kDa (TSPO) from rhodobacter sphaeroides (A139T mutant) in P212121 space group

Structural highlights

4uc2 is a 2 chain structure with sequence from Cereibacter sphaeroides. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.4Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TSPO_CERSP May play a role in the transmembrane transport of tetrapyrroles and similar compounds, and thereby contribute to the regulation of tetrapyrrole biosynthesis (PubMed:10409680). Binds tetrapyrroles and promotes the photooxidative degradation of protoporphyrin IX (PubMed:23651039). Binds protoporphyrin IX, hemin, and coproporphyrin III, but does not bind delta-aminolevulinic acid (PubMed:23952237, PubMed:20541505, PubMed:25635101). Can bind bilirubin, curcumin, gossypol, retinoic acid, cholesterol and the benzodiazepine receptor agonist PK-11195 (in vitro) (PubMed:23952237, PubMed:25635101). Plays a role in the response to low oxygen levels and in the regulation of the biosynthesis of photosynthetic pigments (PubMed:7673149, PubMed:10409680, PubMed:10681549).[1] [2] [3] [4] [5] [6] [7]

Publication Abstract from PubMed

The 18-kilodalton translocator protein (TSPO), proposed to be a key player in cholesterol transport into mitochondria, is highly expressed in steroidogenic tissues, metastatic cancer, and inflammatory and neurological diseases such as Alzheimer's and Parkinson's. TSPO ligands, including benzodiazepine drugs, are implicated in regulating apoptosis and are extensively used in diagnostic imaging. We report crystal structures (at 1.8, 2.4, and 2.5 angstrom resolution) of TSPO from Rhodobacter sphaeroides and a mutant that mimics the human Ala(147)-->Thr(147) polymorphism associated with psychiatric disorders and reduced pregnenolone production. Crystals obtained in the lipidic cubic phase reveal the binding site of an endogenous porphyrin ligand and conformational effects of the mutation. The three crystal structures show the same tightly interacting dimer and provide insights into the controversial physiological role of TSPO and how the mutation affects cholesterol binding.

Protein structure. Crystal structures of translocator protein (TSPO) and mutant mimic of a human polymorphism.,Li F, Liu J, Zheng Y, Garavito RM, Ferguson-Miller S Science. 2015 Jan 30;347(6221):555-8. doi: 10.1126/science.1260590. PMID:25635101[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Yeliseev AA, Kaplan S. TspO of rhodobacter sphaeroides. A structural and functional model for the mammalian peripheral benzodiazepine receptor. J Biol Chem. 2000 Feb 25;275(8):5657-67. PMID:10681549
  2. ↑ Korkhov VM, Sachse C, Short JM, Tate CG. Three-dimensional structure of TspO by electron cryomicroscopy of helical crystals. Structure. 2010 Jun 9;18(6):677-87. doi: 10.1016/j.str.2010.03.001. PMID:20541505 doi:http://dx.doi.org/10.1016/j.str.2010.03.001
  3. ↑ Ginter C, Kiburu I, Boudker O. Chemical catalysis by the translocator protein (18 kDa). Biochemistry. 2013 May 28;52(21):3609-11. doi: 10.1021/bi400364z. Epub 2013 May, 13. PMID:23651039 doi:http://dx.doi.org/10.1021/bi400364z
  4. ↑ Li F, Xia Y, Meiler J, Ferguson-Miller S. Characterization and modeling of the oligomeric state and ligand binding behavior of purified translocator protein 18 kDa from Rhodobacter sphaeroides. Biochemistry. 2013 Aug 27;52(34):5884-99. doi: 10.1021/bi400431t. Epub 2013 Aug, 16. PMID:23952237 doi:http://dx.doi.org/10.1021/bi400431t
  5. ↑ Li F, Liu J, Zheng Y, Garavito RM, Ferguson-Miller S. Protein structure. Crystal structures of translocator protein (TSPO) and mutant mimic of a human polymorphism. Science. 2015 Jan 30;347(6221):555-8. doi: 10.1126/science.1260590. PMID:25635101 doi:http://dx.doi.org/10.1126/science.1260590
  6. ↑ Yeliseev AA, Kaplan S. A sensory transducer homologous to the mammalian peripheral-type benzodiazepine receptor regulates photosynthetic membrane complex formation in Rhodobacter sphaeroides 2.4.1. J Biol Chem. 1995 Sep 8;270(36):21167-75. PMID:7673149
  7. ↑ Yeliseev AA, Kaplan S. A novel mechanism for the regulation of photosynthesis gene expression by the TspO outer membrane protein of Rhodobacter sphaeroides 2.4.1. J Biol Chem. 1999 Jul 23;274(30):21234-43. PMID:10409680
  8. ↑ Li F, Liu J, Zheng Y, Garavito RM, Ferguson-Miller S. Protein structure. Crystal structures of translocator protein (TSPO) and mutant mimic of a human polymorphism. Science. 2015 Jan 30;347(6221):555-8. doi: 10.1126/science.1260590. PMID:25635101 doi:http://dx.doi.org/10.1126/science.1260590

4uc2, resolution 2.40Å

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