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0  structures 1043  species 0  interactions 1274  sequences 6  architectures

Family: TspO_MBR (PF03073)

Summary: TspO/MBR family

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TspO/MBR family Provide feedback

Tryptophan-rich sensory protein (TspO) is an integral membrane protein that acts as a negative regulator of the expression of specific photosynthesis genes in response to oxygen/light [1]. It is involved in the efflux of porphyrin intermediates from the cell. This reduces the activity of coproporphyrinogen III oxidase, which is thought to lead to the accumulation of a putative repressor molecule that inhibits the expression of specific photosynthesis genes. Several conserved aromatic residues are necessary for TspO function: they are thought to be involved in binding porphyrin intermediates [3]. In [2] the rat mitochondrial peripheral benzodiazepine receptor (MBR) was shown to not only retain its structure within a bacterial outer membrane, but also to be able to functionally substitute for TspO in TspO- mutants, and to act in a similar manner to TspO in its in situ location: the outer mitochondrial membrane. The biological significance of MBR remains unclear, however. It is thought to be involved in a variety of cellular functions, including cholesterol transport in steroidogenic tissues.

Literature references

  1. Yeliseev AA, Kaplan S; , J Biol Chem 1995;270:21167-21175.: A sensory transducer homologous to the mammalian peripheral-type benzodiazepine receptor regulates photosynthetic membrane complex formation in Rhodobacter sphaeroides 2.4.1. PUBMED:7673149 EPMC:7673149

  2. Yeliseev AA, Krueger KE, Kaplan S; , Proc Natl Acad Sci U S A 1997;94:5101-5106.: A mammalian mitochondrial drug receptor functions as a bacterial oxygen sensor. PUBMED:9144197 EPMC:9144197

  3. Yeliseev AA, Kaplan S; , J Biol Chem 2000;275:5657-5667.: TspO of rhodobacter sphaeroides. A structural and functional model for the mammalian peripheral benzodiazepine receptor. PUBMED:10681549 EPMC:10681549


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR004307

Members of this group are involved in transmembrane signalling. In both prokaryotes and mitochondria they are localized to the outer membrane, and have been shown to bind and transport dicarboxylic tetrapyrrole intermediates of the haem biosynthetic pathway [PUBMED:1373486, PUBMED:7673149]. They are associated with the major outer membrane porins (in prokaryotes) and with the voltage-dependent anion channel (in mitochondria) [PUBMED:8114671].

Rhodobacter sphaeroides TspO (previously CrtK) 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 [PUBMED:11591680]. 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 [PUBMED:10409680]. A homologue of the TspO protein in Rhizobium meliloti (Sinorhizobium meliloti) is involved in regulating expression of the ndi locus in response to stress conditions [PUBMED:11097914]. There is evidence that the S. meliloti TspO acts through, or in addition to, the FixL regulatory system.

In animals, the peripheral-type benzodiazepine receptor (PBR, MBR) 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 [PUBMED:11806292]. PBR forms a multimeric complex with the voltage-dependent anion channel (VDAC) [PUBMED:8114671] and adenine nucleotide carrier [PUBMED:1373486]. 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 [PUBMED:11158628, PUBMED:12589253].

In complementation experiments, rat PBR (pk18) functionally substitutes for its homologue TspO in R. sphaeroides, negatively affecting transcription of specific photosynthesis genes [PUBMED:9144197]. 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.

Gene Ontology

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Domain organisation

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  Seed
(148)
Full
(1274)
Representative proteomes NCBI
(1142)
Meta
(1226)
RP15
(183)
RP35
(330)
RP55
(441)
RP75
(537)
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  Seed
(148)
Full
(1274)
Representative proteomes NCBI
(1142)
Meta
(1226)
RP15
(183)
RP35
(330)
RP55
(441)
RP75
(537)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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Seed source: Pfam-B_1882 (release 6.4)
Previous IDs: none
Type: Family
Author: Mifsud W
Number in seed: 148
Number in full: 1274
Average length of the domain: 141.80 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 85.38 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.7 20.7
Trusted cut-off 21.2 20.9
Noise cut-off 20.6 20.5
Model length: 148
Family (HMM) version: 10
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