Topological analysis of the peripheral benzodiazepine receptor in yeast mitochondrial membranes supports a five-transmembrane structure
Open accessAbstract
The peripheral benzodiazepine receptor, implicated in the transport of cholesterol from the outer to the inner mitochondrial membrane, is predicted by hydropathy analysis to feature five membrane-spanning domains, with the amino terminus within the mitochondrial periplasm and the carboxyl terminus in the external cytoplasm. We have tested these structural predictions directly by immunodetection of c-Myc-tagged peripheral benzodiazepine receptor on intact yeast mitochondria and by specific labeling in yeast membranes of cysteine residues introduced by site-directed mutagenesis. The combined results support the model originally proposed with some minor but important modifications. The theoretical model predicted relatively short alpha-helical domains, only long enough to span a phospholipid monolayer, whereas the results presented here would support a model with extended alpha-helices sufficiently long to span an entire membrane bilayer, with concomitant shorter loop and tail regions.
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TSPO is predominantly α-helical, containing five helices clustered into a barrel-like shape.
“Biochemical evidence and recent structural determinations of the TSPO protein indicate that TSPO is predominantly α-helical, containing five helices clustered into a barrel-like shape (113–115).”
From Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies (2016) · cites this paper as [113]
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Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies
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Mitochondrial protein import and the genesis of steroidogenic mitochondria
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- Authors
- Joseph-Liauzun, E., Delmas, P., Shire, D., & Ferrara, P.
- Affiliations
- Sanofi (France) (FR)
- Corresponding author
- Joseph-Liauzun, Evelyne
- ORCID
- Shire, David
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-01
- Volume
- 273
- Issue
- 4
- Pages
- 2146-2152
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1982926405
- Cited by
- 102
- References
- 1
- Citations by year
- 2024: 3 · 2021: 2 · 2020: 1 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 7 · 2014: 7 · 2013: 4 · 2012: 10
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- translocator protein (TSPO), yeast mitochondria, cholesterol transport, transmembrane helices, site-directed mutagenesis, hydropathy analysis
- MeSH terms
- Amino Acid Sequence, Biological Transport, Cholesterol, Cysteine, Enzyme-Linked Immunosorbent Assay, Intracellular Membranes, Mitochondria, Molecular Sequence Data, Protein Conformation, Receptors, GABA-A, Saccharomyces cerevisiae, Proto-Oncogene Proteins c-myc, Mutagenesis, Site-Directed, Protein Structure, Secondary, Crystallography, X-Ray, Epitope Mapping
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