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Cited by 317Cholesterol and Lipid MetabolismSteroid Chemistry and BiochemistryLipid Membrane Structure and Behavior

The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.

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

Open access
Li, Hua, Yao, Zhi-xing, Degenhardt, Babett, Teper, Gary, Papadopoulos, Vassilios·2001·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.98.3.1267PMC PMC14743
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Abstract

We previously defined a cholesterol recognition/interaction amino acid consensus (CRAC; AT VL NY Y VW R DNS) in the carboxyl terminus of the peripheral-type benzodiazepine receptor (PBR), an outer mitochondrial membrane protein involved in the regulation of cholesterol transport into the mitochondria, the rate-determining step in steroid biosynthesis. We examined (i) the PBR–cholesterol interaction by UV crosslinking of the C17 side-chain containing progestin, promegestone, and (ii) the role of the CRAC domain of PBR in Leydig cell steroidogenesis by using a transducible peptide composed of the TAT domain of HIV and the CRAC domain of PBR. [ 3 H]Promegestone photoincorporated into recombinant PBR, and this labeling was displaced by cholesterol. [ 3 H]Promegestone also photoincorporated into the TAT-CRAC peptide. [ 3 H]Promegestone crosslinking to TAT-CRAC could be displaced by cholesterol and promegestone, with IC50 values of 1 and 200 μM, respectively. TAT-CRAC efficiently transduced into MA-10 Leydig cells and inhibited the hCG- and cAMP-stimulated steroid production in a dose-dependent manner. TAT-CRAC did not affect the hCG-induced cAMP synthesis and the 22R-hydroxycholesterol-supported steroidogenesis. Mutated TAT-CRAC lost its ability to bind [ 3 H]promegestone and to inhibit the hCG-stimulated steroidogenesis. These results show that TAT-CRAC binds cholesterol and competes for cholesterol interaction with endogenous PBR, suggesting that the cytosolic carboxyl-terminal domain of PBR is responsible for taking up and bringing steroidogenic cholesterol into the mitochondria.

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Crossref · 10.1073/pnas.98.3.1267

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  • TSPO contains an evolutionarily conserved C-terminal CRAC motif that facilitates cholesterol binding through a conserved tyrosine residue.

    “TSPO does contain an evolutionarily conserved C-terminal cholesterol recognition amino acid concensus (CRAC) motif (117, 118), which has been shown to facilitate cholesterol binding through a conserved tyrosine residue (119).”

    From Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies (2016) · cites this paper as [119]

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Research works printed but not linked: 7

  1. V Papadopoulos Endocr Rev 14, 222–240 (1993).
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  3. H Miettinen, J Kononen, H Haapasalo, P Helen, P Sallinen, T Harjuntausta, H Helin, H Alho Cancer Res 55, 2691–2695 (1995).
  4. J D Hirsch, C F Beyer, L Malkowitz, B Beer, A J Blume Mol Pharmacol 35, 157–163 (1989).
  5. V Papadopoulos, A Kapsis, H Li, H Amri, M Hardwick, M Culty, P G Kasprzyk, M Carlson, J Moreau, K Drieu Anticancer Res 20, 2835–2848 (2000).
  6. 10.1210/endo.139.12.6390 · DOI · Paper page
  7. D R Gius, S A Ezhevsky, M Becker-Hapak, H Nagahara, M C Wei, S F Dowdy Cancer Res 59, 2577–2580 (1999).

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Metadata

Authors
Li, H., Yao, Z.-X., Degenhardt, B., Teper, G., & Papadopoulos, V.
Affiliations
  • Georgetown University (US)
  • Division of Hormone Research, Departments of Cell Biology and Pharmacology and Neuroscience, Georgetown University School of Medicine, Washington, DC. 20007
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2001-01-23
Volume
98
Issue
3
Pages
1267-1272
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.98.3.1267
PMC
PMC14743
OpenAlex
W2142761929
Cited by
317
References
28
Citations by year
2026: 4 · 2025: 9 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 18 · 2020: 15 · 2019: 5 · 2018: 11 · 2017: 12 · 2016: 16 · 2015: 15 · 2014: 19 · 2013: 14 · 2012: 21
FWCI
17.21
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Environmental Health Sciences (R01ES007747, ES 07747)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
  • Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
translocator protein (TSPO), cholesterol binding, steroidogenesis inhibition, HIV TAT peptide, promegestone, Leydig cells, mitochondrial cholesterol transport, mitochondrial outer membrane proteins
MeSH terms
Amino Acid Sequence, Animals, Binding Sites, Cell Line, Cholesterol, Cloning, Molecular, HIV, Kinetics, Leydig Cells, Male, Mitochondria, Molecular Sequence Data, Progesterone, Promegestone, Receptors, GABA-A, Recombinant Proteins, Tritium, Gene Products, tat, Consensus Sequence, Mice, tat Gene Products, Human Immunodeficiency Virus

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