Biology:Disulfide oxidoreductase D
| Disulfide bond oxidoreductase D | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | DsbD | ||||||||
| Pfam | PF02683 | ||||||||
| TCDB | 5.A.1 | ||||||||
| OPM superfamily | 248 | ||||||||
| OPM protein | 2n4x | ||||||||
| |||||||||
The Disulfide bond oxidoreductase D (DsbD) family is a member of the Lysine Exporter (LysE) Superfamily.[1] A representative list of proteins belonging to the DsbD family can be found in the Transporter Classification Base.
Homology
Homologues include:
(1) several thiol-disulfide exchange proteins (i.e., TC# 5.A.1.1.1)
(2) the cytochrome c-type biogenesis proteins, CcdA (TC# 5.A.1.2.1) of Paracoccus pantotrophus and Bacillus subtilis.[2][3]
(3) the methylamine utilization proteins, MauF (TC# 5.A.1.3.1) of Paracoccus denitrificans and P. versutus.[4][5]
(4) the mercury resistance proteins (TC# 5.A.1.4.1; possibly Hg2+ transporters) of Mycobacterium tuberculosis and Streptomyces lividans.[6][7]
(5) suppressors of copper sensitivity (TC# 5.A.1.5.1; copper tolerance proteins) of Salmonella typhimurium and Vibrio cholerae.[8][9]
(6) components of peroxide reduction pathways (TC# 5.A.1.5.2), 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).[10][11] 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.[11] 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.
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).[12]
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.[11] 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).[10] 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, NO−3 or fumarate).
See also
References
- ↑ "The LysE Superfamily of Transport Proteins Involved in Cell Physiology and Pathogenesis". PLOS ONE 10 (10): e0137184. 2015-01-01. doi:10.1371/journal.pone.0137184. PMID 26474485. Bibcode: 2015PLoSO..1037184T.
- ↑ "Identification of ccdA in Paracoccus pantotrophus GB17: disruption of ccdA causes complete deficiency in c-type cytochromes". Journal of Bacteriology 183 (1): 257–63. January 2001. doi:10.1128/JB.183.1.257-263.2001. PMID 11114924.
- ↑ "Genes required for cytochrome c synthesis in Bacillus subtilis". Molecular Microbiology 36 (3): 638–50. May 2000. doi:10.1046/j.1365-2958.2000.01883.x. PMID 10844653.
- ↑ "The genetic organization of the mau gene cluster of the facultative autotroph Paracoccus denitrificans". Biochemical and Biophysical Research Communications 184 (3): 1181–9. May 1992. doi:10.1016/s0006-291x(05)80007-5. PMID 1590782.
- ↑ "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 226 (1): 201–10. November 1994. doi:10.1111/j.1432-1033.1994.tb20042.x. PMID 7957249.
- ↑ "Regulation of the operon responsible for broad-spectrum mercury resistance in Streptomyces lividans 1326". Molecular & General Genetics 251 (3): 307–15. June 1996. doi:10.1007/bf02172521. PMID 8676873.
- ↑ "Cloning and DNA sequence analysis of the mercury resistance genes of Streptomyces lividans". Molecular & General Genetics 236 (1): 76–85. December 1992. doi:10.1007/BF00279645. PMID 1494353.
- ↑ "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: 148–51. July 1996. PMID 8783519.
- ↑ "A Salmonella typhimurium genetic locus which confers copper tolerance on copper-sensitive mutants of Escherichia coli". Journal of Bacteriology 179 (16): 4977–84. August 1997. doi:10.1128/jb.179.16.4977-4984.1997. PMID 9260936.
- ↑ 10.0 10.1 "Transmembrane electron transfer by the membrane protein DsbD occurs via a disulfide bond cascade". Cell 103 (5): 769–79. November 2000. doi:10.1016/s0092-8674(00)00180-x. PMID 11114333.
- ↑ 11.0 11.1 11.2 "DsbD-catalyzed transport of electrons across the membrane of Escherichia coli". The Journal of Biological Chemistry 276 (5): 3696–701. February 2001. doi:10.1074/jbc.M009500200. PMID 11085993.
- ↑ "Structure and multistate function of the transmembrane electron transporter CcdA". Nature Structural & Molecular Biology 22 (10): 809–14. October 2015. doi:10.1038/nsmb.3099. PMID 26389738.
Further reading
- "Identification of ccdA in Paracoccus pantotrophus GB17: disruption of ccdA causes complete deficiency in c-type cytochromes". Journal of Bacteriology 183 (1): 257–63. January 2001. doi:10.1128/JB.183.1.257-263.2001. PMID 11114924.
- "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): 5066–76. July 2006. doi:10.1128/JB.00368-06. PMID 16816179.
- "Oxidative protein folding in bacteria". Molecular Microbiology 44 (1): 1–8. April 2002. doi:10.1046/j.1365-2958.2002.02851.x. PMID 11967064. https://deepblue.lib.umich.edu/bitstream/2027.42/75150/1/j.1365-2958.2002.02851.x.pdf.
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