Tryptophan-rich sensory protein

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TspO_MBR
Identifiers
Symbol TspO_MBR
Pfam PF03073
InterPro IPR004307
TCDB Manning Peyton Manning
CDD cd15904

Tryptophan-rich sensory proteins (TspO) are a family of proteins that are involved in transmembrane signalling. In either prokaryotes or mitochondria they are localized to the outer membrane, and have been shown to bind and transport dicarboxylic tetrapyrrole intermediates of the haem biosynthetic pathway.[1][2] They are associated with the major outer membrane porins (in prokaryotes) and with the voltage-dependent anion channel (in mitochondria).[3]

TspO of Rhodobacter sphaeroides is involved in signal transduction, functioning as a negative regulator of the expression of some photosynthesis genes (PpsR/AppA repressor/antirepressor regulon). This down-regulation is believed to be in response to oxygen levels. TspO works through (or modulates) the PpsR/AppA system and acts upstream of the site of action of these regulatory proteins.[4] It has been suggested that the TspO regulatory pathway works by regulating the efflux of certain tetrapyrrole intermediates of the haem/bacteriochlorophyll biosynthetic pathways in response to the availability of molecular oxygen, thereby causing the accumulation of a biosynthetic intermediate that serves as a corepressor for the regulated genes.[5] A homologue of the TspO protein in Rhizobium meliloti is involved in regulating expression of the ndi locus in response to stress conditions.[6]

In animals, the peripheral benzodiazepine receptor is a mitochondrial protein (located in the outer mitochondrial membrane) characterised by its ability to bind with nanomolar affinity to a variety of benzodiazepine-like drugs, as well as to dicarboxylic tetrapyrrole intermediates of the haem biosynthetic pathway. Depending upon the tissue, it was shown to be involved in steroidogenesis, haem biosynthesis, apoptosis, cell growth and differentiation, mitochondrial respiratory control, and immune and stress response, but the precise function of the PBR remains unclear. The role of PBR in the regulation of cholesterol transport from the outer to the inner mitochondrial membrane, the rate-determining step in steroid biosynthesis, has been studied in detail. PBR is required for the binding, uptake and release, upon ligand activation, of the substrate cholesterol.[7] PBR forms a multimeric complex with the voltage-dependent anion channel (VDAC) [3] and adenine nucleotide carrier.[1] Molecular modeling of PBR suggested that it might function as a channel for cholesterol. Indeed, cholesterol uptake and transport by bacterial cells was induced upon PBR expression. Mutagenesis studies identified a cholesterol recognition/interaction motif (CRAC) in the cytoplasmic C terminus of PBR.[8][9]

In complementation experiments, rat PBR (pk18) protein functionally substitutes for its homologue TspO in R. sphaeroides, negatively affecting transcription of specific photosynthesis genes.[10] This suggests that PBR may function as an oxygen sensor, transducing an oxygen-triggered signal leading to an adaptive cellular response.

These observations suggest that fundamental aspects of this receptor and the downstream signal transduction pathway are conserved in bacteria and higher eukaryotic mitochondria. The alpha-3 subdivision of the purple bacteria is considered to be a likely source of the endosymbiont that ultimately gave rise to the mitochondrion. Therefore, it is possible that the mammalian PBR remains both evolutionarily and functionally related to the TspO of R. sphaeroides.

References[edit]

  1. ^ a b McEnery MW, Snowman AM, Trifiletti RR, Snyder SH (April 1992). "Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier". Proc. Natl. Acad. Sci. U.S.A. 89 (8): 3170–4. doi:10.1073/pnas.89.8.3170. PMC 48827Freely accessible. PMID 1373486. 
  2. ^ Yeliseev AA, Kaplan S (September 1995). "A sensory transducer homologous to the mammalian peripheral-type benzodiazepine receptor regulates photosynthetic membrane complex formation in Rhodobacter sphaeroides 2.4.1". J. Biol. Chem. 270 (36): 21167–75. doi:10.1074/jbc.270.36.21167. PMID 7673149. 
  3. ^ a b Garnier M, Dimchev AB, Boujrad N, Price JM, Musto NA, Papadopoulos V (February 1994). "In vitro reconstitution of a functional peripheral-type benzodiazepine receptor from mouse Leydig tumor cells". Mol. Pharmacol. 45 (2): 201–11. PMID 8114671. 
  4. ^ Zeng X, Kaplan S (November 2001). "TspO as a modulator of the repressor/antirepressor (PpsR/AppA) regulatory system in Rhodobacter sphaeroides 2.4.1". J. Bacteriol. 183 (21): 6355–64. doi:10.1128/JB.183.21.6355-6364.2001. PMC 100131Freely accessible. PMID 11591680. 
  5. ^ Yeliseev AA, Kaplan S (July 1999). "A novel mechanism for the regulation of photosynthesis gene expression by the TspO outer membrane protein of Rhodobacter sphaeroides 2.4.1". J. Biol. Chem. 274 (30): 21234–43. doi:10.1074/jbc.274.30.21234. PMID 10409680. 
  6. ^ Davey ME, de Bruijn FJ (December 2000). "A homologue of the tryptophan-rich sensory protein TspO and FixL regulate a novel nutrient deprivation-induced Sinorhizobium meliloti locus". Appl. Environ. Microbiol. 66 (12): 5353–9. doi:10.1128/aem.66.12.5353-5359.2000. PMC 92468Freely accessible. PMID 11097914. 
  7. ^ Papadopoulos V, Amri H, Li H, Yao Z, Brown RC, Vidic B, Culty M (2001). "Structure, function and regulation of the mitochondrial peripheral-type benzodiazepine receptor". Therapie. 56 (5): 549–56. PMID 11806292. 
  8. ^ Li H, Yao Z, Degenhardt B, Teper G, Papadopoulos V (January 2001). "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". Proc. Natl. Acad. Sci. U.S.A. 98 (3): 1267–72. doi:10.1073/pnas.031461598. PMC 14743Freely accessible. PMID 11158628. 
  9. ^ Papadopoulos V (January 2003). "Peripheral benzodiazepine receptor: structure and function in health and disease". Ann Pharm Fr. 61 (1): 30–50. PMID 12589253. 
  10. ^ Yeliseev AA, Krueger KE, Kaplan S (May 1997). "A mammalian mitochondrial drug receptor functions as a bacterial "oxygen" sensor". Proc. Natl. Acad. Sci. U.S.A. 94 (10): 5101–6. doi:10.1073/pnas.94.10.5101. PMC 24638Freely accessible. PMID 9144197. 

This article incorporates text from the public domain Pfam and InterPro IPR004307