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- W2013250768 abstract "The mitochondrial outer membrane protein Translocator Protein 18 kDa (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), has been proposed to be a key component of the cholesterol transport system in mitochondria and a rate limiting step for steroidogenesis. Dysregulation of neurosteroids generation involving TSPO has been shown to be related to a variety of neurological and psychiatric diseases, including Alzheimer's disease, Parkinson's disease, as well as bipolar disorder. In addition, ligands of TSPO are widely used for imaging brain injury and inflammation, areas in which TSPO is highly expressed. A natural human single-nucleotide polymorphism (SNP) gives rise to a mutation, A147T, within the proposed cholesterol recognition site (CRAC). This mutation leads to altered ligand binding and has recently been reported to reduce pregnenolone production and to be associated with bipolar disorder. The same mutation is reported to inhibit a proposed TSPO catalyzed degradation of prototoporphyrin IX. TSPO from Rhodobacter sphaeroides (RsTSPO) shares high sequence similarity with the human protein but differs in the region of the SNP and shows significantly lower cholesterol binding. To better understand the interaction of TSPO with cholesterol, porphyrin and other ligands, we expressed and purified the recombinant RsTSPO and several mutants in the cholesterol binding region. Binding properties were investigated with a sensitive tryptophan fluorescence quenching assay and the interactions were characterized by X-ray crystallography.(Supported by the MSU Center for Mitochondrial Science and Medicine, a Strategic Partnership Grant from Michigan State University Foundation and GM26916 to SFM)." @default.
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- W2013250768 date "2014-01-01" @default.
- W2013250768 modified "2023-10-18" @default.
- W2013250768 title "Characterization of Cholesterol and Drug Ligand Interactions with Translocator Protein 18 KDA (TSPO) from Rhodobacter Sphaeroides" @default.
- W2013250768 doi "https://doi.org/10.1016/j.bpj.2013.11.128" @default.
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