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Escherichia coli K-12 substr. MG1655 Polypeptide: protein disulfide oxidoreductase - DsbDreduced



Gene: dsbD Accession Numbers: EG12178 (EcoCyc), b4136, ECK4130

Synonyms: htrI, cutA2, cycZ, dipZ, DsbDreduced, thiol:disulfide interchange protein DsbD, inner membrane copper tolerance protein

Regulation Summary Diagram: ?

Alternative forms of protein disulfide oxidoreductase - DsbDreduced: protein disulfide oxidoreductase - DsbDoxidized

Summary:
DsbD is an inner membrane protein that transfers electrons from cytoplasmic thioredoxin to the periplasmic substrate proteins DsbC and DsbG and to the cytochrome c biogenesis protein CcmG. DsbD consists of three domains: a periplasmic N-terminal domain (nDsbD or DsbDα) which contains an immunoglobulin-like fold, a central transmembrane (TM) domain (tmDsbD) with eight predicted TM helices and a periplasmic C-terminal domain (cDsbD or DsbDγ) which contains a thioredoxin-like fold [Missiakas95, Crooke95, Goulding02].

The electron cascade is initiated with the reduction of tmDsbD by thioredoxin, cDsbD then shuttles electrons from tmDsbD to nDsbD and reduced nDsbD passes the electrons on to the periplasmic substrate proteins [Gordon00, Chung00a, Katzen00]. DsbD is capable of shuffling electrons from the cytoplasm to the periplasm without the involvement of additional cofactors such as quinone, FAD or heme [Rozhkova08]. Transfer of electrons across the membrane is thought to occur via thiol disulfide exchange reactions involving the two redox active cysteines contained in each of the three domains of DsbD and reaction intermediates containing mixed disulfide complexes have been isolated [Katzen03, Cho07, Cho09].

Overexpression of dsbD results in phenotypes (loss of motility and alkaline phosphatase activity) that are consistent with the misfolding/reduction of periplasmic proteins containing disulfide bonds [Missiakas95]. dsbD mutants display defects in alkaline phosphatase folding which can be complemented by the addition of reduced dithiothreitol (DTT) [Rietsch96]. dsbD mutants accumulate oxidised DsbC [Rietsch97] and oxidised DsbG [Bessette99]. The purified C-terminal domain of DsbD is able to reduce insulin in the presence of DTT [Missiakas95]. dsbD is essential for growth at temperatures above 42oC [Missiakas95].

Reviews: [Fabianek00, Porat04a, Stirnimann06].

Citations: [Mavridou11, Stirnimann05, Stirnimann06a, Rozhkova07, Rozhkova04, Haebel02, Haebel01, Goldstone01, Kim03a, Fong95, Sambongi94]

Gene Citations: [Stewart99a]

Locations: inner membrane

Map Position: [4,361,368 <- 4,363,065] (94.0 centisomes)
Length: 1698 bp / 565 aa

Molecular Weight of Polypeptide: 61.795 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0013539 , CGSC:34213 , DIP:DIP-9476N , EchoBASE:EB2095 , EcoGene:EG12178 , EcoliWiki:b4136 , IAF1260:2703935 , ModBase:P36655 , OU-Microarray:b4136 , PortEco:dipZ , PR:PRO_000022482 , Pride:P36655 , Protein Model Portal:P36655 , RegulonDB:EG12178 , SMR:P36655 , String:511145.b4136 , UniProt:P36655

Relationship Links: InterPro:IN-FAMILY:IPR003834 , InterPro:IN-FAMILY:IPR012336 , InterPro:IN-FAMILY:IPR017937 , InterPro:IN-FAMILY:IPR022910 , InterPro:IN-FAMILY:IPR028250 , Panther:IN-FAMILY:PTHR32234 , Panther:IN-FAMILY:PTHR32234:SF1 , PDB:Structure:1JPE , PDB:Structure:1JZD , PDB:Structure:1L6P , PDB:Structure:1VRS , PDB:Structure:1Z5Y , PDB:Structure:2FWE , PDB:Structure:2FWF , PDB:Structure:2FWG , PDB:Structure:2FWH , PDB:Structure:3PFU , PDB:Structure:41P6 , PDB:Structure:4IP1 , Pfam:IN-FAMILY:PF02683 , Pfam:IN-FAMILY:PF11412 , Prosite:IN-FAMILY:PS00194 , Prosite:IN-FAMILY:PS51352

In Paralogous Gene Group: 389 (2 members)

In Reactions of unknown directionality:

Not in pathways:
DsbGoxidized[periplasmic space] + DsbDreduced[periplasmic space] = DsbGreduced[periplasmic space] + DsbDoxidized[periplasmic space]
DsbDreduced[periplasmic space] + DsbCoxidized[periplasmic space] = DsbDoxidized[periplasmic space] + DsbCreduced[periplasmic space]

GO Terms:

Biological Process: GO:0017004 - cytochrome complex assembly Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA06, GOA01a, Sambongi94]
GO:0042493 - response to drug Inferred from experiment [Missiakas95]
GO:0045454 - cell redox homeostasis Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, Missiakas95]
GO:0055085 - transmembrane transport Inferred from experiment [Katzen00]
GO:0055114 - oxidation-reduction process Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA06, GOA01a, Missiakas95]
GO:0071502 - cellular response to temperature stimulus Inferred from experiment [Missiakas95]
Molecular Function: GO:0015035 - protein disulfide oxidoreductase activity Inferred from experiment [Rietsch96, Missiakas95]
GO:0016491 - oxidoreductase activity Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Rietsch96, Missiakas95]
GO:0022865 - transmembrane electron transfer carrier Inferred from experiment [Katzen00]
GO:0009055 - electron carrier activity Inferred by computational analysis [GOA06]
GO:0047134 - protein-disulfide reductase activity Inferred by computational analysis [GOA06, GOA01, GOA01a]
Cellular Component: GO:0005887 - integral component of plasma membrane Inferred from experiment [Cho09]
GO:0005886 - plasma membrane Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, GOA06, Missiakas95]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11a, Missiakas95]

MultiFun Terms: cell structure membrane
metabolism biosynthesis of macromolecules (cellular constituents) large molecule carriers cytochromes
metabolism metabolism of other compounds sulfur metabolism

Essentiality data for dsbD knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Credits:
Last-Curated ? 08-Feb-2012 by Mackie A , Macquarie University


Sequence Features

Feature Class Location Citations Comment
Signal-Sequence 1 -> 19
[Chung00a, UniProt11a]
.
Mutagenesis-Variant 13
[Stewart99a, UniProt11a]
Alternate sequence: C → A; UniProt: No loss of activity.
Chain 20 -> 565
[UniProt09]
UniProt: Thiol:disulfide interchange protein dsbD;
Mutagenesis-Variant 122
[Stewart99a, Chung00a, Gordon00, UniProt11a]
Alternate sequence: C → A; UniProt: Loss of activity.
Disulfide-Bond-Site 128, 122
[UniProt10a]
UniProt: Redox-active; Non-Experimental Qualifier: probable;
Mutagenesis-Variant 128
[Stewart99a, Chung00a, Gordon00, UniProt11a]
Alternate sequence: C → A; UniProt: Loss of activity.
Transmembrane-Region 163 -> 183
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Mutagenesis-Variant 182
[Stewart99a, Chung00a, Gordon00, UniProt11a]
Alternate sequence: C → A; UniProt: Loss of activity.
Disulfide-Bond-Site 304, 182
[UniProt10a]
UniProt: Redox-active; Non-Experimental Qualifier: probable;
Transmembrane-Region 208 -> 228
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 243 -> 263
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 296 -> 316
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Mutagenesis-Variant 301
[Stewart99a, Chung00a, Gordon00, UniProt11a]
Alternate sequence: C → A; UniProt: No loss of activity.
Mutagenesis-Variant 304
[Stewart99a, Chung00a, Gordon00, UniProt11a]
Alternate sequence: C → A; UniProt: Loss of activity.
Transmembrane-Region 323 -> 343
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 357 -> 377
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 384 -> 404
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 418 -> 438
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Conserved-Region 434 -> 565
[UniProt09]
UniProt: Thioredoxin;
Mutagenesis-Variant 480
[Stewart99a, Chung00a, Gordon00, UniProt11a]
Alternate sequence: C → A; UniProt: Loss of activity; when associated with A-483.
Disulfide-Bond-Site 483, 480
[UniProt10a]
UniProt: Redox-active; Non-Experimental Qualifier: probable;
Mutagenesis-Variant 483
[Stewart99a, Chung00a, Gordon00, UniProt11a]
Alternate sequence: C → A; UniProt: Loss of activity; when associated with A-480.


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
10/20/97 Gene b4136 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG12178; confirmed by SwissProt match.


References

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Bessette99: Bessette PH, Cotto JJ, Gilbert HF, Georgiou G (1999). "In vivo and in vitro function of the Escherichia coli periplasmic cysteine oxidoreductase DsbG." J Biol Chem 1999;274(12);7784-92. PMID: 10075670

Cho07: Cho SH, Porat A, Ye J, Beckwith J (2007). "Redox-active cysteines of a membrane electron transporter DsbD show dual compartment accessibility." EMBO J 26(15);3509-20. PMID: 17641688

Cho09: Cho SH, Beckwith J (2009). "Two snapshots of electron transport across the membrane: insights into the structure and function of DsbD." J Biol Chem 284(17);11416-24. PMID: 19258316

Chung00a: Chung J, Chen T, Missiakas D (2000). "Transfer of electrons across the cytoplasmic membrane by DsbD, a membrane protein involved in thiol-disulphide exchange and protein folding in the bacterial periplasm." Mol Microbiol 2000;35(5);1099-109. PMID: 10712691

Crooke95: Crooke H, Cole J (1995). "The biogenesis of c-type cytochromes in Escherichia coli requires a membrane-bound protein, DipZ, with a protein disulphide isomerase-like domain." Mol Microbiol 1995;15(6);1139-50. PMID: 7623667

Fabianek00: Fabianek RA, Hennecke H, Thony-Meyer L (2000). "Periplasmic protein thiol:disulfide oxidoreductases of Escherichia coli." FEMS Microbiol Rev 2000;24(3);303-16. PMID: 10841975

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Fong95: Fong ST, Camakaris J, Lee BT (1995). "Molecular genetics of a chromosomal locus involved in copper tolerance in Escherichia coli K-12." Mol Microbiol 1995;15(6);1127-37. PMID: 7623666

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Goldstone01: Goldstone D, Haebel PW, Katzen F, Bader MW, Bardwell JC, Beckwith J, Metcalf P (2001). "DsbC activation by the N-terminal domain of DsbD." Proc Natl Acad Sci U S A 98(17);9551-6. PMID: 11493705

Gordon00: Gordon EH, Page MD, Willis AC, Ferguson SJ (2000). "Escherichia coli DipZ: anatomy of a transmembrane protein disulphide reductase in which three pairs of cysteine residues, one in each of three domains, contribute differentially to function." Mol Microbiol 35(6);1360-74. PMID: 10760137

Goulding02: Goulding CW, Sawaya MR, Parseghian A, Lim V, Eisenberg D, Missiakas D (2002). "Thiol-disulfide exchange in an immunoglobulin-like fold: structure of the N-terminal domain of DsbD." Biochemistry 41(22);6920-7. PMID: 12033924

Haebel01: Haebel PW, Wichman S, Goldstone D, Metcalf P (2001). "Crystallization and initial crystallographic analysis of the disulfide bond isomerase DsbC in complex with the alpha domain of the electron transporter DsbD." J Struct Biol 136(2);162-6. PMID: 11886218

Haebel02: Haebel PW, Goldstone D, Katzen F, Beckwith J, Metcalf P (2002). "The disulfide bond isomerase DsbC is activated by an immunoglobulin-fold thiol oxidoreductase: crystal structure of the DsbC-DsbDalpha complex." EMBO J 21(18);4774-84. PMID: 12234918

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Katzen00: Katzen F, Beckwith J (2000). "Transmembrane electron transfer by the membrane protein DsbD occurs via a disulfide bond cascade." Cell 103(5);769-79. PMID: 11114333

Katzen03: Katzen F, Beckwith J (2003). "Role and location of the unusual redox-active cysteines in the hydrophobic domain of the transmembrane electron transporter DsbD." Proc Natl Acad Sci U S A 100(18);10471-6. PMID: 12925743

Kim03a: Kim JH, Kim SJ, Jeong DG, Son JH, Ryu SE (2003). "Crystal structure of DsbDgamma reveals the mechanism of redox potential shift and substrate specificity(1)." FEBS Lett 543(1-3);164-9. PMID: 12753926

Mavridou11: Mavridou DA, Saridakis E, Kritsiligkou P, Goddard AD, Stevens JM, Ferguson SJ, Redfield C (2011). "Oxidation state-dependent protein-protein interactions in disulfide cascades." J Biol Chem 286(28);24943-56. PMID: 21543317

Missiakas95: Missiakas D, Schwager F, Raina S (1995). "Identification and characterization of a new disulfide isomerase-like protein (DsbD) in Escherichia coli." EMBO J 1995;14(14);3415-24. PMID: 7628442

Porat04a: Porat A, Cho SH, Beckwith J (2004). "The unusual transmembrane electron transporter DsbD and its homologues: a bacterial family of disulfide reductases." Res Microbiol 155(8);617-22. PMID: 15380548

Rietsch96: Rietsch A, Belin D, Martin N, Beckwith J (1996). "An in vivo pathway for disulfide bond isomerization in Escherichia coli." Proc Natl Acad Sci U S A 93(23);13048-53. PMID: 8917542

Rietsch97: Rietsch A, Bessette P, Georgiou G, Beckwith J (1997). "Reduction of the periplasmic disulfide bond isomerase, DsbC, occurs by passage of electrons from cytoplasmic thioredoxin." J Bacteriol 1997;179(21);6602-8. PMID: 9352906

Rozhkova04: Rozhkova A, Stirnimann CU, Frei P, Grauschopf U, Brunisholz R, Grutter MG, Capitani G, Glockshuber R (2004). "Structural basis and kinetics of inter- and intramolecular disulfide exchange in the redox catalyst DsbD." EMBO J 23(8);1709-19. PMID: 15057279

Rozhkova07: Rozhkova A, Glockshuber R (2007). "Kinetics of the intramolecular disulfide exchange between the periplasmic domains of DsbD." J Mol Biol 367(4);1162-70. PMID: 17303162

Rozhkova08: Rozhkova A, Glockshuber R (2008). "Thermodynamic aspects of DsbD-mediated electron transport." J Mol Biol 380(5);783-8. PMID: 18571669

Sambongi94: Sambongi Y, Ferguson SJ (1994). "Specific thiol compounds complement deficiency in c-type cytochrome biogenesis in Escherichia coli carrying a mutation in a membrane-bound disulphide isomerase-like protein." FEBS Lett 1994;353(3);235-8. PMID: 7957865

Stewart99a: Stewart EJ, Katzen F, Beckwith J (1999). "Six conserved cysteines of the membrane protein DsbD are required for the transfer of electrons from the cytoplasm to the periplasm of Escherichia coli." EMBO J 18(21);5963-71. PMID: 10545108

Stirnimann05: Stirnimann CU, Rozhkova A, Grauschopf U, Grutter MG, Glockshuber R, Capitani G (2005). "Structural basis and kinetics of DsbD-dependent cytochrome c maturation." Structure 13(7);985-93. PMID: 16004871

Stirnimann06: Stirnimann CU, Grutter MG, Glockshuber R, Capitani G (2006). "nDsbD: a redox interaction hub in the Escherichia coli periplasm." Cell Mol Life Sci 63(14);1642-8. PMID: 16786221

Stirnimann06a: Stirnimann CU, Rozhkova A, Grauschopf U, Bockmann RA, Glockshuber R, Capitani G, Grutter MG (2006). "High-resolution structures of Escherichia coli cDsbD in different redox states: A combined crystallographic, biochemical and computational study." J Mol Biol 358(3);829-45. PMID: 16545842

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt11a: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."


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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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