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.
| Disulfide bond oxidoreductase D | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | DsbD | ||||||||
| Pfam | PF02683 | ||||||||
| TCDB | 5.A.1 | ||||||||
| OPM superfamily | 248 | ||||||||
| OPM protein | 2n4x | ||||||||
| |||||||||
Homology
editHomologues 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)
editThe 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
editDsbB 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
editIn 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
editDsbD 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
editReferences
edit- ^ Tsu BV, Saier MH (2015-01-01). "The LysE Superfamily of Transport Proteins Involved in Cell Physiology and Pathogenesis". PLOS ONE. 10 (10): e0137184. Bibcode:2015PLoSO..1037184T. doi:10.1371/journal.pone.0137184. PMC 4608589. PMID 26474485.
- ^ Bardischewsky F, Friedrich CG (January 2001). "Identification of ccdA in Paracoccus pantotrophus GB17: disruption of ccdA causes complete deficiency in c-type cytochromes". Journal of Bacteriology. 183 (1): 257–63. doi:10.1128/JB.183.1.257-263.2001. PMC 94873. PMID 11114924.
- ^ Le Brun NE, Bengtsson J, Hederstedt L (May 2000). "Genes required for cytochrome c synthesis in Bacillus subtilis". Molecular Microbiology. 36 (3): 638–50. doi:10.1046/j.1365-2958.2000.01883.x. PMID 10844653. S2CID 25023629.
- ^ Chistoserdov AY, Boyd J, Mathews FS, Lidstrom ME (May 1992). "The genetic organization of the mau gene cluster of the facultative autotroph Paracoccus denitrificans". Biochemical and Biophysical Research Communications. 184 (3): 1181–9. doi:10.1016/s0006-291x(05)80007-5. PMID 1590782.
- ^ Van Spanning RJ, van der Palen CJ, Slotboom DJ, Reijnders WN, Stouthamer AH, Duine JA (November 1994). "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. doi:10.1111/j.1432-1033.1994.tb20042.x. PMID 7957249.
- ^ Brünker P, Rother D, Sedlmeier R, Klein J, Mattes R, Altenbuchner J (June 1996). "Regulation of the operon responsible for broad-spectrum mercury resistance in Streptomyces lividans 1326". Molecular & General Genetics. 251 (3): 307–15. doi:10.1007/bf02172521. PMID 8676873. S2CID 9810136.
- ^ Sedlmeier R, Altenbuchner J (December 1992). "Cloning and DNA sequence analysis of the mercury resistance genes of Streptomyces lividans". Molecular & General Genetics. 236 (1): 76–85. doi:10.1007/BF00279645. PMID 1494353. S2CID 12103057.
- ^ Choudhury P, Kumar R (July 1996). "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. PMID 8783519.
- ^ Gupta SD, Wu HC, Rick PD (August 1997). "A Salmonella typhimurium genetic locus which confers copper tolerance on copper-sensitive mutants of Escherichia coli". Journal of Bacteriology. 179 (16): 4977–84. doi:10.1128/jb.179.16.4977-4984.1997. PMC 179352. PMID 9260936.
- ^ a b Katzen F, Beckwith J (November 2000). "Transmembrane electron transfer by the membrane protein DsbD occurs via a disulfide bond cascade". Cell. 103 (5): 769–79. doi:10.1016/s0092-8674(00)00180-x. PMID 11114333. S2CID 9362819.
- ^ a b c Krupp R, Chan C, Missiakas D (February 2001). "DsbD-catalyzed transport of electrons across the membrane of Escherichia coli". The Journal of Biological Chemistry. 276 (5): 3696–701. doi:10.1074/jbc.M009500200. PMID 11085993.
- ^ Williamson JA, Cho SH, Ye J, Collet JF, Beckwith JR, Chou JJ (October 2015). "Structure and multistate function of the transmembrane electron transporter CcdA". Nature Structural & Molecular Biology. 22 (10): 809–14. doi:10.1038/nsmb.3099. PMC 7871232. PMID 26389738. S2CID 21521855.
Further reading
edit- Bardischewsky F, Friedrich CG (January 2001). "Identification of ccdA in Paracoccus pantotrophus GB17: disruption of ccdA causes complete deficiency in c-type cytochromes". Journal of Bacteriology. 183 (1): 257–63. doi:10.1128/JB.183.1.257-263.2001. PMC 94873. PMID 11114924.
- Cho SH, Beckwith J (July 2006). "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. doi:10.1128/JB.00368-06. PMC 1539965. PMID 16816179.
- Collet JF, Bardwell JC (April 2002). "Oxidative protein folding in bacteria" (PDF). Molecular Microbiology. 44 (1): 1–8. doi:10.1046/j.1365-2958.2002.02851.x. hdl:2027.42/75150. PMID 11967064. S2CID 15339428.
