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U.S.A."],"published-print":{"date-parts":[[2001,1,30]]},"abstract":"<jats:p>\n            We previously defined a cholesterol recognition\/interaction amino\n acid consensus (CRAC;\n AT\n            <jats:underline>VL<\/jats:underline>\n            NY\n            <jats:underline>Y<\/jats:underline>\n            VW\n            <jats:underline>R<\/jats:underline>\n            DNS) in the carboxyl\n terminus of the peripheral-type benzodiazepine receptor (PBR), an outer\n mitochondrial membrane protein involved in the regulation of\n cholesterol transport into the mitochondria, the rate-determining step\n in steroid biosynthesis. We examined (i) the PBR\u2013cholesterol\n interaction by UV crosslinking of the C17 side-chain containing\n progestin, promegestone, and (ii) the role of the CRAC domain of PBR in\n Leydig cell steroidogenesis by using a transducible peptide composed of\n the TAT domain of HIV and the CRAC domain of PBR.\n [\n            <jats:sup>3<\/jats:sup>\n            H]Promegestone photoincorporated into recombinant PBR,\n and this labeling was displaced by cholesterol.\n [\n            <jats:sup>3<\/jats:sup>\n            H]Promegestone also photoincorporated into the TAT-CRAC\n peptide. [\n            <jats:sup>3<\/jats:sup>\n            H]Promegestone crosslinking to TAT-CRAC could\n be displaced by cholesterol and promegestone, with IC50 values of 1 and\n 200 \u03bcM, respectively. TAT-CRAC efficiently transduced into MA-10\n Leydig cells and inhibited the hCG- and cAMP-stimulated steroid\n production in a dose-dependent manner. TAT-CRAC did not affect the\n hCG-induced cAMP synthesis and the 22R-hydroxycholesterol-supported\n steroidogenesis. Mutated TAT-CRAC lost its ability to bind\n [\n            <jats:sup>3<\/jats:sup>\n            H]promegestone and to inhibit the hCG-stimulated\n steroidogenesis. These results show that TAT-CRAC binds cholesterol and\n competes for cholesterol interaction with endogenous PBR,\n suggesting that the cytosolic carboxyl-terminal domain of PBR is\n responsible for taking up and bringing steroidogenic cholesterol into\n the mitochondria.\n          <\/jats:p>","DOI":"10.1073\/pnas.98.3.1267","type":"journal-article","created":{"date-parts":[[2012,7,26]],"date-time":"2012-07-26T23:06:14Z","timestamp":1343343974000},"page":"1267-1272","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":285,"title":["Cholesterol binding at the cholesterol recognition\/ interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide"],"prefix":"10.1073","volume":"98","author":[{"given":"Hua","family":"Li","sequence":"first","affiliation":[{"name":"Division of Hormone Research, Departments of Cell Biology and\r Pharmacology and Neuroscience, Georgetown University\r School of Medicine, Washington, DC. 20007"}]},{"given":"Zhi-xing","family":"Yao","sequence":"additional","affiliation":[{"name":"Division of Hormone Research, Departments of Cell Biology and\r Pharmacology and Neuroscience, Georgetown University\r School of Medicine, Washington, DC. 20007"}]},{"given":"Babett","family":"Degenhardt","sequence":"additional","affiliation":[{"name":"Division of Hormone Research, Departments of Cell Biology and\r Pharmacology and Neuroscience, Georgetown University\r School of Medicine, Washington, DC. 20007"}]},{"given":"Gary","family":"Teper","sequence":"additional","affiliation":[{"name":"Division of Hormone Research, Departments of Cell Biology and\r Pharmacology and Neuroscience, Georgetown University\r School of Medicine, Washington, DC. 20007"}]},{"given":"Vassilios","family":"Papadopoulos","sequence":"additional","affiliation":[{"name":"Division of Hormone Research, Departments of Cell Biology and\r Pharmacology 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