TSPO (protein)
| TSPO (protein) | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 169 amino acids | |
| Secondary to quaternary structure | multipass membrane protein | |
| Identifier | ||
| Gene names | TSPO ; BZRP | |
| External IDs | ||
| Transporter classification | ||
| TCDB | 9.C.6.1.1 | |
| designation | Mitochondrial outer membrane uptake pathway | |
| Occurrence | ||
| Parent taxon | Euteleostomi | |
TSTU (abbr. Of Engl. T ran s locator P r o tein , or T ryptophan-rich s ensory p r o t on ), also known as peripheral benzodiazepine receptor ( PBR ) is a transmembrane protein of the outer mitochondrial membrane with a molecular weight from 18 kDa. TSPO, like the GABA receptor, binds benzodiazepines .
In addition to many other functions, it is involved in the regulation of the biosynthesis of steroid hormones and porphyrins and plays a role in apoptosis . TSPO was discovered in 1977 while looking for binding sites for diazepam in peripheral tissues.
The nucleotide sequence is highly conserved and encodes a membrane protein with probably five transmembrane helices . Homologous proteins are found in bacteria, plants and animals. For a long time it was not possible to create a knockout mouse . In cells without the TSPO gene, protoporphyrin IX accumulates in the mitochondria, so it was assumed that the protein is essential for life. In 2015 it was possible to generate knockout mice. A knockout moss in which one of these genes has been switched off is viable but susceptible to stress.
Functions
There is evidence of at least two main functions of TSPO: cholesterol binding, followed by cholesterol transport, and porphyrin binding and transport.
Steroid hormone biosynthesis
The polypeptide DBI ( D iazepam- b inding- i nhibitor ) interacts with the TSPO and stimulate pregnenolone formation in the mitochondria. The biosynthesis of all steroid hormones and neurosteroids takes place via pregnenolone. Other TSPO ligands also stimulate steroid hormone biosynthesis and neurosteroid biosynthesis. The TSPO mediates the transport of cholesterol from the outer to the inner membrane of the mitochondria. This leads to an increased metabolism of cholesterol. The side chain- splitting enzyme, a cytochrome P450 , is located in the matrix of the mitochondria , which forms pregnenolone from cholesterol by splitting off isocapronal.
Porphyrin transport and heme biosynthesis
Hembiosynthesis also takes place in the mitochondria . Here the TSPO mediates the import of the precursor coproporphyrinogen III. From this the heme is formed in the mitochondrial matrix via the intermediate stages protoporphyrinogen IX, protoporphyrin IX by inserting the central iron ion.
Individual evidence
- ↑ UniProt P30536
- ↑ Papadopoulos, V. et al. (2006): Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. In: Trends Pharmacol. Sci. 27 (8), 402-409. PMID 16822554 .
- ↑ Casellas, P. et al. (2002): Peripheral benzodiazepine receptors and mitochondrial function. In: Neurochem. Int. 40 (6), 475-486. PMID 11850104
- ↑ Taketani, S. et al. (1995): Involvement of peripheral-type benzodiazepine receptors in the intracellular transport of heme and porphyrins. In: J. Biochem. 117 (4), 875-880. PMID 7592553
- ↑ Braestrup, C. & Squires, RF (1977): Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H) diazepam binding. In: Proc. Natl. Acad. Sci. USA 74 (9): 3805-3809. PMID 20632
- ↑ Bernassau, JM et al. (1993): A 3D model of the peripheral benzodiazepine receptor and its implication in intra mitochondrial cholesterol transport. In: J. Mol. Graph. 11 (4), 236-244. PMID 8136326
- ↑ Zeno S, Veenman L, Katz Y, Bode J, Gavish M, and Zaaroor, M. (2012) The 18 kDa mitochondrial translocator protein (TSPO) prevents accumulation of protoporphyrin IX. Involvement of reactive oxygen species (ROS). Curr Mol Med 12, 494-501. PMID 22376065
- ↑ Zhao AH, Tu LN, Mukai C, Sirivelu MP, Pillai VV, Morohaku K, Cohen R, Selvaraj V. Mitochondrial translocator protein (TSPO) function is not essential for heme biosynthesis. J Biol Chem 2015 ;: jbc.M115.686360-31. PMID 26627829
- ↑ Frank W, Baar KM, Qudeimat E, Woriedh M, Alawady A, Ratnadewi D, Gremillon L, Grimm B, Reski R (2007): A mitochondrial protein homologous to the mammalian peripheral-type benzodiazepine receptor is essential for stress adaptation in plants . Plant Journal 51, 1004-1018. PMID 17651369