4uc1
High resolution crystal structure of translocator protein 18kDa (TSPO) from Rhodobacter sphaeroides (A139T Mutant) in C2 space group
Structural highlights
FunctionTSPO_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 PubMedThe 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
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