Summary: Cytochrome C biogenesis protein transmembrane region
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This is the Wikipedia entry entitled "Disulfide oxidoreductase D". More...
Disulfide oxidoreductase D Edit Wikipedia article
The Disufide Bond Oxidoreductase D (DsbD) Family (TC# 5.A.1) is a member of the Lysine Exporter (LysE) Superfamily. A representative list of proteins belonging to the DsbD family can be found in the Transporter Classification Base.
Homology
Homologues include:
(1) several thiol-disufide exchange proteins
(2) the cytochrome c-type biogenesis proteins, CcdA of Paracoccus pantotrophus and Bacillus subtilis.[1][2]Â
(3) the methylamine utilization proteins, MauF (TC# 5.A.1.3.1) of Paracoccus denitrificans and P. versutus.[3][4]Â
(4) the mercury resistance proteins (possibly Hg2+ transporters) of Mycobacterium tuberculosis and Streptomyces lividans.[5][6]Â
(5) suppressors of copper sensitivity (copper tolerance proteins) of Salmonella typhimurium and Vibrio cholerae.[7][8]Â
(6) components of peroxide reduction pathways, and
(7) components of sulfenic acid reductases.
Disulfide Bond Oxidoreductase D (DsbD)
The best characterized member of the DsbD family is DsbD of E. coli (TC# 5.A.1.1.1).[9][10] The DsbD protein is membrane-embedded with a putative N-terminal transmembrane segment (TMS) plus 8 additionalTMSs. The smallest homologues (190 aas with 6 putative TMSs) are found in archaea, while the largest are found in both Gram-negative bacteria (758 aas with 9 putative TMSs) and Gram-positive bacteria (695 aas with 6 putative TMSs).
The overall vectorial electron transfer reaction catalyzed by DsbD is:
2 e-cytoplasm → 2 e-periplasm
Structure
DsbB contains 4 essential cysteine residues, reversibly forming two disulfide bonds. Although DsbA displays no proofreading activity for repair of wrongly paired disulfides, DsbC, DsbE and DsbG have been found to demonstrate proofreading activity.[10] Therefore, the two transmembrane pathways involving DsbD and DsbB together catalyze extracellular disulfide reduction (DsbD) and oxidation (DsbB) in a superficially reversible process that allows dithiol/disulfide exchange.
Crystal Structures
Several crystal structures are available for DsbD and related proteins. A representative list of these structures can be found in the Transporter Classification Database or in RCSB.
Some of these PDB structures include: PDB: 1JZD​, 1L6P​, 1VRS​, 2FWE​, 2FWF​, 2FWG​, 3PFU​, 4IP1​, 4IP6​
System Reduction Pathway
In the E. coli DsbD system, electrons are transferred from NADPH in the cytoplasm to periplasmic dithiol/disulfide-containing proteins via an electron transfer chain that sequentially involves NADPH, thioredoxin reductase (TrxB; present in the cytoplasm), thioredoxin (TrxA; also in the cytoplasm), DsbD (the integral membrane constituent of the system), and the periplasmic electron acceptors (DsbC, DsbE (CcmG) and DsbG).[11]
All of these last three proteins (DsbC, DsbE (CcmG) and DsbG) can donate electrons to oxidized disulfide-containing proteins in the periplasm of a Gram-negative bacterium or presumably in the external milieu of a Gram-positive bacterium or an archaeon.
Thus, the pathway is:
NADPH → TrxB → TrxA → DsbD → (DsbC, DsbE, or DsbG) → proteins.
DsbD contains three cysteine pairs that undergo reversible disulfide rearrangements.[10] TrxA donates electrons to the transmembrane cysteines C163 (C3) and C285 (C5) in putative TMSs 1 and 4 in the DsbD model proposed by Katzen and Beckwith (2000).[9] This dithiol then donates electrons to the periplasmic C-terminal thioredoxin motif (CXXC) of DsbD, thereby reducing C461 and C464 (C6 and C7, respectively). This dithiol pair attacks the periplasmic N-terminal disulfide bridge at C103 and C109 (C1 and C2, respectively) which transfers electrons to DsbC and other protein electron acceptors as noted above.
Reverse Pathway
DsbD catalyses an essentially irreversible reaction due to the fact that electrons flow down their electrochemical gradient from inside the cell (negative inside) to outside the cell (positive outside). In order to reverse the reaction, electrons are transferred from dithiol proteins in the periplasm to an electron acceptor in the cytoplasm as follows:
reduced proteinperiplasm → DsbAperiplasm → DsbBmembrane → quinonesmembrane → reductasemembrane→ terminal electron acceptorcytoplasm (e.g., O2, NO3- or fumarate).
See Also
Further Reading
- Bardischewsky, F.; Friedrich, C. G. (2001-01-01)."Identification of ccdA in Paracoccus pantotrophus GB17: disruption of ccdA causes complete deficiency in c-type cytochromes". Journal of Bacteriology 183 (1): 257–263.doi:10.1128/JB.183.1.257-263.2001. ISSN 0021-9193.PMC 94873. PMID 11114924.
- Cho, Seung-Hyun; Beckwith, Jon (2006-07-01)."Mutations of the membrane-bound disulfide reductase DsbD that block electron transfer steps from cytoplasm to periplasm in Escherichia coli". Journal of Bacteriology 188(14): 5066–5076. doi:10.1128/JB.00368-06. ISSN 0021-9193. PMC 1539965. PMID 16816179.
- Collet, Jean-Francois; Bardwell, James C. A. (2002-04-01). "Oxidative protein folding in bacteria".Molecular Microbiology 44 (1): 1–8. ISSN 0950-382X.PMID 11967064.
References
- ^ Bardischewsky, F.; Friedrich, C. G. (2001-01-01). "Identification of ccdA in Paracoccus pantotrophus GB17: disruption of ccdA causes complete deficiency in c-type cytochromes". Journal of Bacteriology. 183 (1): 257–263. doi:10.1128/JB.183.1.257-263.2001. ISSN 0021-9193. PMC 94873. PMID 11114924.
- ^ Le Brun, N. E.; Bengtsson, J.; Hederstedt, L. (2000-05-01). "Genes required for cytochrome c synthesis in Bacillus subtilis". Molecular Microbiology. 36 (3): 638–650. ISSN 0950-382X. PMID 10844653.
- ^ Chistoserdov, A. Y.; Boyd, J.; Mathews, F. S.; Lidstrom, M. E. (1992-05-15). "The genetic organization of the mau gene cluster of the facultative autotroph Paracoccus denitrificans". Biochemical and Biophysical Research Communications. 184 (3): 1181–1189. ISSN 0006-291X. PMID 1590782.
- ^ Van Spanning, R. J.; van der Palen, C. J.; Slotboom, D. J.; Reijnders, W. N.; Stouthamer, A. H.; Duine, J. A. (1994-11-15). "Expression of the mau genes involved in methylamine metabolism in Paracoccus denitrificans is under control of a LysR-type transcriptional activator". European journal of biochemistry / FEBS. 226 (1): 201–210. ISSN 0014-2956. PMID 7957249.
- ^ Brünker, P.; Rother, D.; Sedlmeier, R.; Klein, J.; Mattes, R.; Altenbuchner, J. (1996-06-12). "Regulation of the operon responsible for broad-spectrum mercury resistance in Streptomyces lividans 1326". Molecular & general genetics: MGG. 251 (3): 307–315. ISSN 0026-8925. PMID 8676873.
- ^ Sedlmeier, R.; Altenbuchner, J. (1992-12-01). "Cloning and DNA sequence analysis of the mercury resistance genes of Streptomyces lividans". Molecular & general genetics: MGG. 236 (1): 76–85. ISSN 0026-8925. PMID 1494353.
- ^ Choudhury, P.; Kumar, R. (1996-07-01). "Association of metal tolerance with multiple antibiotic resistance of enteropathogenic organisms isolated from coastal region of deltaic Sunderbans". The Indian Journal of Medical Research. 104: 148–151. ISSN 0971-5916. PMID 8783519.
- ^ Gupta, S. D.; Wu, H. C.; Rick, P. D. (1997-08-01). "A Salmonella typhimurium genetic locus which confers copper tolerance on copper-sensitive mutants of Escherichia coli". Journal of Bacteriology. 179 (16): 4977–4984. ISSN 0021-9193. PMC 179352. PMID 9260936.
- ^ a b Katzen, F.; Beckwith, J. (2000-11-22). "Transmembrane electron transfer by the membrane protein DsbD occurs via a disulfide bond cascade". Cell. 103 (5): 769–779. ISSN 0092-8674. PMID 11114333.
- ^ a b c Krupp, R.; Chan, C.; Missiakas, D. (2001-02-02). "DsbD-catalyzed transport of electrons across the membrane of Escherichia coli". The Journal of Biological Chemistry. 276 (5): 3696–3701. doi:10.1074/jbc.M009500200. ISSN 0021-9258. PMID 11085993.
- ^ Williamson, Jessica A.; Cho, Seung-Hyun; Ye, Jiqing; Collet, Jean-Francois; Beckwith, Jonathan R.; Chou, James J. (2015-10-01). "Structure and multistate function of the transmembrane electron transporter CcdA". Nature Structural & Molecular Biology. 22 (10): 809–814. doi:10.1038/nsmb.3099. ISSN 1545-9985. PMID 26389738.
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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Cytochrome C biogenesis protein transmembrane region Provide feedback
This family consists of the transmembrane (i.e. non-catalytic) region of Cytochrome C biogenesis proteins also known as disulphide interchange proteins. These proteins posses a protein disulphide isomerase like domain that is not found within the aligned region of this family.
Literature references
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Crooke H, Cole J; , Mol Microbiol 1995;15:1139-1150.: The biogenesis of c-type cytochromes in Escherichia coli requires a membrane-bound protein, DipZ, with a protein disulphide isomerase-like domain. PUBMED:7623667 EPMC:7623667
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Missiakas D, Schwager F, Raina S; , EMBO J 1995;14:3415-3424.: Identification and characterization of a new disulfide isomerase-like protein (DsbD) in Escherichia coli. PUBMED:7628442 EPMC:7628442
Internal database links
| SCOOP: | DsbD_2 LysE NicO SfLAP |
| Similarity to PfamA using HHSearch: | DsbD_2 |
External database links
| Transporter classification: | 5.A.1 |
This tab holds annotation information from the InterPro database.
InterPro entry IPR003834
This entry represents the transmembrane domain of Cytochrome C biogenesis proteins also known as disulphide interchange proteins, such as DsbD from E. coli and DipZ from Mycobacterium. These proteins posses a protein disulphide isomerase like domain that is not found within the aligned region of this family.
DsbA and DsbC, periplasmic proteins of E. coli, are two key players involved in disulphide bond formation. DsbD generates a reducing source in the periplasm, which is required for maintaining proper redox conditions [ PUBMED:7628442 ]. DipZ is essential for maintaining cytochrome c apoproteins in the correct conformations for the covalent attachment of haem groups to the appropriate pairs of cysteine residues [ PUBMED:7623667 ].
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Cellular component | membrane (GO:0016020) |
| Biological process | cytochrome complex assembly (GO:0017004) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan LysE (CL0292), which has the following description:
This clan includes a diverse range of transporter families [1].
The clan contains the following 19 members:
BacA Cad Colicin_V DsbD DsbD_2 DUF475 DUF6044 FTR1 HupE_UreJ HupE_UreJ_2 LysE MarC Mntp NicO OFeT_1 SfLAP TauE TerC UPF0016Alignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
| Seed (7) |
Full (10963) |
Representative proteomes | UniProt (58030) |
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| RP15 (1310) |
RP35 (5117) |
RP55 (11435) |
RP75 (20129) |
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| PP/heatmap | 1 | ||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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| Seed (7) |
Full (10963) |
Representative proteomes | UniProt (58030) |
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|---|---|---|---|---|---|---|---|
| RP15 (1310) |
RP35 (5117) |
RP55 (11435) |
RP75 (20129) |
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| Raw Stockholm | |||||||
| Gzipped | |||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | COG0785 |
| Previous IDs: | none |
| Type: | Family |
| Sequence Ontology: | SO:0100021 |
| Author: |
Bashton M  , Bateman A , Eberhardt R
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| Number in seed: | 7 |
| Number in full: | 10963 |
| Average length of the domain: | 203.3 aa |
| Average identity of full alignment: | 24 % |
| Average coverage of the sequence by the domain: | 51.31 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 213 | ||||||||||||
| Family (HMM) version: | 18 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Colour assignments
Archea
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Eukaryota
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Viruses
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Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the DsbD domain has been found. There are 1 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.
