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PDBsum entry 2b5e
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* Residue conservation analysis
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Enzyme class:
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E.C.5.3.4.1
- protein disulfide-isomerase.
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Reaction:
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Rearrangement of both intrachain and interchain disulfide bonds in proteins to form the native structures.
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DOI no:
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Cell
124:61-73
(2006)
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PubMed id:
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The crystal structure of yeast protein disulfide isomerase suggests cooperativity between its active sites.
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G.Tian,
S.Xiang,
R.Noiva,
W.J.Lennarz,
H.Schindelin.
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ABSTRACT
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Protein disulfide isomerase plays a key role in catalyzing the folding of
secretory proteins. It features two catalytically inactive thioredoxin domains
inserted between two catalytically active thioredoxin domains and an acidic
C-terminal tail. The crystal structure of yeast PDI reveals that the four
thioredoxin domains are arranged in the shape of a twisted "U" with
the active sites facing each other across the long sides of the "U."
The inside surface of the "U" is enriched in hydrophobic residues,
thereby facilitating interactions with misfolded proteins. The domain
arrangement, active site location, and surface features strikingly resemble the
Escherichia coli DsbC and DsbG protein disulfide isomerases. Biochemical studies
demonstrate that all domains of PDI, including the C-terminal tail, are required
for full catalytic activity. The structure defines a framework for rationalizing
the differences between the two active sites and their respective roles in
catalyzing the formation and rearrangement of disulfide bonds.
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Selected figure(s)
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Figure 4.
Figure 4. Hydrophobic Surface Features of PDI
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Figure 5.
Figure 5. Active Site Features of PDI
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2006,
124,
61-73)
copyright 2006.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.Riemer,
H.G.Hansen,
C.Appenzeller-Herzog,
L.Johansson,
and
L.Ellgaard
(2011).
Identification of the PDI-Family Member ERp90 as an Interaction Partner of ERFAD.
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PLoS One,
6,
e17037.
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J.Winter,
S.Gleiter,
P.Klappa,
and
H.Lilie
(2011).
Protein disulfide isomerase isomerizes non-native disulfide bonds in human proinsulin independent of its peptide-binding activity.
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Protein Sci,
20,
588-596.
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K.D.Tew,
and
D.M.Townsend
(2011).
Regulatory functions of glutathione S-transferase P1-1 unrelated to detoxification.
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Drug Metab Rev,
43,
179-193.
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L.A.Rutkevich,
and
D.B.Williams
(2011).
Participation of lectin chaperones and thiol oxidoreductases in protein folding within the endoplasmic reticulum.
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Curr Opin Cell Biol,
23,
157-166.
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M.Hagiwara,
K.Maegawa,
M.Suzuki,
R.Ushioda,
K.Araki,
Y.Matsumoto,
J.Hoseki,
K.Nagata,
and
K.Inaba
(2011).
Structural basis of an ERAD pathway mediated by the ER-resident protein disulfide reductase ERdj5.
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Mol Cell,
41,
432-444.
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PDB codes:
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W.Zheng,
Y.Chu,
Q.Yin,
L.Xu,
C.Yang,
W.Zhang,
Y.Tang,
and
Y.Yang
(2011).
Crucial effect of the first CXXC motif of human QSOX 1b on the activity to different substrates.
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J Biochem,
149,
293-300.
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A.Van Hateren,
E.James,
A.Bailey,
A.Phillips,
N.Dalchau,
and
T.Elliott
(2010).
The cell biology of major histocompatibility complex class I assembly: towards a molecular understanding.
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Tissue Antigens,
76,
259-275.
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C.Wang,
S.Chen,
X.Wang,
L.Wang,
A.K.Wallis,
R.B.Freedman,
and
C.C.Wang
(2010).
Plasticity of human protein disulfide isomerase: evidence for mobility around the X-linker region and its functional significance.
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J Biol Chem,
285,
26788-26797.
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D.P.Sideris,
and
K.Tokatlidis
(2010).
Oxidative protein folding in the mitochondrial intermembrane space.
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Antioxid Redox Signal,
13,
1189-1204.
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E.Pedone,
D.Limauro,
K.D'Ambrosio,
G.De Simone,
and
S.Bartolucci
(2010).
Multiple catalytically active thioredoxin folds: a winning strategy for many functions.
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Cell Mol Life Sci,
67,
3797-3814.
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E.d'Aloisio,
A.R.Paolacci,
A.P.Dhanapal,
O.A.Tanzarella,
E.Porceddu,
and
M.Ciaffi
(2010).
The Protein Disulfide Isomerase gene family in bread wheat (T. aestivum L.).
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BMC Plant Biol,
10,
101.
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G.Kozlov,
P.Määttänen,
D.Y.Thomas,
and
K.Gehring
(2010).
A structural overview of the PDI family of proteins.
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FEBS J,
277,
3924-3936.
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H.Dong,
S.Qin,
and
H.X.Zhou
(2010).
Effects of macromolecular crowding on protein conformational changes.
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PLoS Comput Biol,
6,
e1000833.
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J.F.Collet,
and
J.Messens
(2010).
Structure, function, and mechanism of thioredoxin proteins.
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Antioxid Redox Signal,
13,
1205-1216.
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K.Inaba
(2010).
Structural basis of protein disulfide bond generation in the cell.
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Genes Cells,
15,
935-943.
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K.Inaba,
S.Masui,
H.Iida,
S.Vavassori,
R.Sitia,
and
M.Suzuki
(2010).
Crystal structures of human Ero1α reveal the mechanisms of regulated and targeted oxidation of PDI.
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EMBO J,
29,
3330-3343.
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PDB codes:
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L.A.Rutkevich,
M.F.Cohen-Doyle,
U.Brockmeier,
and
D.B.Williams
(2010).
Functional relationship between protein disulfide isomerase family members during the oxidative folding of human secretory proteins.
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Mol Biol Cell,
21,
3093-3105.
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S.M.Rizvi,
and
M.Raghavan
(2010).
Mechanisms of function of tapasin, a critical major histocompatibility complex class I assembly factor.
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Traffic,
11,
332-347.
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V.K.Kodali,
and
C.Thorpe
(2010).
Quiescin sulfhydryl oxidase from Trypanosoma brucei: catalytic activity and mechanism of a QSOX family member with a single thioredoxin domain.
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Biochemistry,
49,
2075-2085.
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V.K.Kodali,
and
C.Thorpe
(2010).
Oxidative protein folding and the Quiescin-sulfhydryl oxidase family of flavoproteins.
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Antioxid Redox Signal,
13,
1217-1230.
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Z.Wang,
Z.Zhou,
Z.Y.Guo,
and
C.W.Chi
(2010).
Snapshot of the interaction between HIV envelope glycoprotein 120 and protein disulfide isomerase.
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Acta Biochim Biophys Sin (Shanghai),
42,
358-362.
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A.K.Wallis,
A.Sidhu,
L.J.Byrne,
M.J.Howard,
L.W.Ruddock,
R.A.Williamson,
and
R.B.Freedman
(2009).
The ligand-binding b' domain of human protein disulphide-isomerase mediates homodimerization.
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Protein Sci,
18,
2569-2577.
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A.Y.Denisov,
P.Määttänen,
C.Dabrowski,
G.Kozlov,
D.Y.Thomas,
and
K.Gehring
(2009).
Solution structure of the bb' domains of human protein disulfide isomerase.
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FEBS J,
276,
1440-1449.
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PDB code:
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C.W.Gruber,
M.Cemazar,
A.Mechler,
L.L.Martin,
and
D.J.Craik
(2009).
Biochemical and biophysical characterization of a novel plant protein disulfide isomerase.
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Biopolymers,
92,
35-43.
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D.M.Townsend,
Y.Manevich,
L.He,
Y.Xiong,
R.R.Bowers,
S.Hutchens,
and
K.D.Tew
(2009).
Nitrosative stress-induced s-glutathionylation of protein disulfide isomerase leads to activation of the unfolded protein response.
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Cancer Res,
69,
7626-7634.
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D.Ramadan,
P.C.Rancy,
R.P.Nagarkar,
J.P.Schneider,
and
C.Thorpe
(2009).
Arsenic(III) species inhibit oxidative protein folding in vitro.
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Biochemistry,
48,
424-432.
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F.Hatahet,
and
L.W.Ruddock
(2009).
Protein disulfide isomerase: a critical evaluation of its function in disulfide bond formation.
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Antioxid Redox Signal,
11,
2807-2850.
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G.Dong,
P.A.Wearsch,
D.R.Peaper,
P.Cresswell,
and
K.M.Reinisch
(2009).
Insights into MHC class I peptide loading from the structure of the tapasin-ERp57 thiol oxidoreductase heterodimer.
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Immunity,
30,
21-32.
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PDB code:
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G.Kozlov,
P.Määttänen,
J.D.Schrag,
G.L.Hura,
L.Gabrielli,
M.Cygler,
D.Y.Thomas,
and
K.Gehring
(2009).
Structure of the noncatalytic domains and global fold of the protein disulfide isomerase ERp72.
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Structure,
17,
651-659.
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PDB code:
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H.J.Atkinson,
and
P.C.Babbitt
(2009).
An atlas of the thioredoxin fold class reveals the complexity of function-enabling adaptations.
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PLoS Comput Biol,
5,
e1000541.
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J.Riemer,
N.Bulleid,
and
J.M.Herrmann
(2009).
Disulfide formation in the ER and mitochondria: two solutions to a common process.
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Science,
324,
1284-1287.
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M.Kurz,
I.Iturbe-Ormaetxe,
R.Jarrott,
S.R.Shouldice,
M.A.Wouters,
P.Frei,
R.Glockshuber,
S.L.O'Neill,
B.Heras,
and
J.L.Martin
(2009).
Structural and functional characterization of the oxidoreductase alpha-DsbA1 from Wolbachia pipientis.
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Antioxid Redox Signal,
11,
1485-1500.
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PDB codes:
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M.L.Forster,
J.J.Mahn,
and
B.Tsai
(2009).
Generating an Unfoldase from Thioredoxin-like Domains.
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J Biol Chem,
284,
13045-13056.
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S.A.Arredondo,
T.F.Chen,
A.F.Riggs,
H.F.Gilbert,
and
G.Georgiou
(2009).
Role of dimerization in the catalytic properties of the Escherichia coli disulfide isomerase DsbC.
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J Biol Chem,
284,
23972-23979.
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S.Lee,
B.Park,
K.Kang,
and
K.Ahn
(2009).
Redox-regulated export of the major histocompatibility complex class I-peptide complexes from the endoplasmic reticulum.
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Mol Biol Cell,
20,
3285-3294.
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T.Nakamura,
and
S.A.Lipton
(2009).
Cell death: protein misfolding and neurodegenerative diseases.
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Apoptosis,
14,
455-468.
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X.Lou,
R.Bao,
C.Z.Zhou,
and
Y.Chen
(2009).
Structure of the thioredoxin-fold domain of human phosducin-like protein 2.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
65,
67-70.
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PDB code:
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Y.Kim,
K.Kang,
I.Kim,
Y.J.Lee,
C.Oh,
J.Ryoo,
E.Jeong,
and
K.Ahn
(2009).
Molecular mechanisms of MHC class I-antigen processing: redox considerations.
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Antioxid Redox Signal,
11,
907-936.
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Y.Zhang,
G.Kozlov,
C.L.Pocanschi,
U.Brockmeier,
B.S.Ireland,
P.Maattanen,
C.Howe,
T.Elliott,
K.Gehring,
and
D.B.Williams
(2009).
ERp57 does not require interactions with calnexin and calreticulin to promote assembly of class I histocompatibility molecules, and it enhances peptide loading independently of its redox activity.
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J Biol Chem,
284,
10160-10173.
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A.Fraldi,
E.Zito,
F.Annunziata,
A.Lombardi,
M.Cozzolino,
M.Monti,
C.Spampanato,
A.Ballabio,
P.Pucci,
R.Sitia,
and
M.P.Cosma
(2008).
Multistep, sequential control of the trafficking and function of the multiple sulfatase deficiency gene product, SUMF1 by PDI, ERGIC-53 and ERp44.
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Hum Mol Genet,
17,
2610-2621.
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B.S.Mamathambika,
and
J.C.Bardwell
(2008).
Disulfide-linked protein folding pathways.
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Annu Rev Cell Dev Biol,
24,
211-235.
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C.Appenzeller-Herzog,
and
L.Ellgaard
(2008).
In vivo reduction-oxidation state of protein disulfide isomerase: the two active sites independently occur in the reduced and oxidized forms.
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Antioxid Redox Signal,
10,
55-64.
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D.R.Peaper,
and
P.Cresswell
(2008).
Regulation of MHC class I assembly and peptide binding.
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Annu Rev Cell Dev Biol,
24,
343-368.
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E.J.Heckler,
P.C.Rancy,
V.K.Kodali,
and
C.Thorpe
(2008).
Generating disulfides with the Quiescin-sulfhydryl oxidases.
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Biochim Biophys Acta,
1783,
567-577.
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E.Pedone,
D.Limauro,
and
S.Bartolucci
(2008).
The machinery for oxidative protein folding in thermophiles.
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Antioxid Redox Signal,
10,
157-170.
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F.R.Laurindo,
D.C.Fernandes,
A.M.Amanso,
L.R.Lopes,
and
C.X.Santos
(2008).
Novel role of protein disulfide isomerase in the regulation of NADPH oxidase activity: pathophysiological implications in vascular diseases.
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Antioxid Redox Signal,
10,
1101-1113.
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G.Hernández,
J.S.Anderson,
and
D.M.LeMaster
(2008).
Electrostatic stabilization and general base catalysis in the active site of the human protein disulfide isomerase a domain monitored by hydrogen exchange.
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Chembiochem,
9,
768-778.
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G.Tian,
F.X.Kober,
U.Lewandrowski,
A.Sickmann,
W.J.Lennarz,
and
H.Schindelin
(2008).
The Catalytic Activity of Protein-disulfide Isomerase Requires a Conformationally Flexible Molecule.
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J Biol Chem,
283,
33630-33640.
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PDB code:
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L.Wang,
L.Wang,
S.Vavassori,
S.Li,
H.Ke,
T.Anelli,
M.Degano,
R.Ronzoni,
R.Sitia,
F.Sun,
and
C.C.Wang
(2008).
Crystal structure of human ERp44 shows a dynamic functional modulation by its carboxy-terminal tail.
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EMBO Rep,
9,
642-647.
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PDB code:
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R.Ladenstein,
and
B.Ren
(2008).
Reconsideration of an early dogma, saying "there is no evidence for disulfide bonds in proteins from archaea".
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Extremophiles,
12,
29-38.
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S.Arredondo,
L.Segatori,
H.F.Gilbert,
and
G.Georgiou
(2008).
De Novo Design and Evolution of Artificial Disulfide Isomerase Enzymes Analogous to the Bacterial DsbC.
|
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J Biol Chem,
283,
31469-31476.
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S.Gleiter,
and
J.C.Bardwell
(2008).
Disulfide bond isomerization in prokaryotes.
|
| |
Biochim Biophys Acta,
1783,
530-534.
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T.Kimura,
T.Horibe,
C.Sakamoto,
Y.Shitara,
F.Fujiwara,
T.Komiya,
A.Yamamoto,
T.Hayano,
N.Takahashi,
and
M.Kikuchi
(2008).
Evidence for mitochondrial localization of P5, a member of the protein disulphide isomerase family.
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| |
J Biochem,
144,
187-196.
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T.Nakamura,
and
S.A.Lipton
(2008).
Emerging roles of s-nitrosylation in protein misfolding and neurodegenerative diseases.
|
| |
Antioxid Redox Signal,
10,
87.
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A.Becerra,
L.Delaye,
A.Lazcano,
and
L.E.Orgel
(2007).
Protein disulfide oxidoreductases and the evolution of thermophily: was the last common ancestor a heat-loving microbe?
|
| |
J Mol Evol,
65,
296-303.
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A.Kozarova,
I.Sliskovic,
B.Mutus,
E.S.Simon,
P.C.Andrews,
and
P.O.Vacratsis
(2007).
Identification of redox sensitive thiols of protein disulfide isomerase using isotope coded affinity technology and mass spectrometry.
|
| |
J Am Soc Mass Spectrom,
18,
260-269.
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B.Heras,
M.Kurz,
S.R.Shouldice,
and
J.L.Martin
(2007).
The name's bond......disulfide bond.
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| |
Curr Opin Struct Biol,
17,
691-698.
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C.Grillo,
C.D'Ambrosio,
V.Consalvi,
R.Chiaraluce,
A.Scaloni,
M.Maceroni,
M.Eufemi,
and
F.Altieri
(2007).
DNA-binding activity of the ERp57 C-terminal domain is related to a redox-dependent conformational change.
|
| |
J Biol Chem,
282,
10299-10310.
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C.W.Gruber,
M.Cemazar,
R.J.Clark,
T.Horibe,
R.F.Renda,
M.A.Anderson,
and
D.J.Craik
(2007).
A novel plant protein-disulfide isomerase involved in the oxidative folding of cystine knot defense proteins.
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| |
J Biol Chem,
282,
20435-20446.
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D.M.Monroe,
and
N.S.Key
(2007).
The tissue factor-factor VIIa complex: procoagulant activity, regulation, and multitasking.
|
| |
J Thromb Haemost,
5,
1097-1105.
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F.Hatahet,
and
L.W.Ruddock
(2007).
Substrate recognition by the protein disulfide isomerases.
|
| |
FEBS J,
274,
5223-5234.
|
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J.Haugstetter,
M.A.Maurer,
T.Blicher,
M.Pagac,
G.Wider,
and
L.Ellgaard
(2007).
Structure-function analysis of the endoplasmic reticulum oxidoreductase TMX3 reveals interdomain stabilization of the N-terminal redox-active domain.
|
| |
J Biol Chem,
282,
33859-33867.
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K.O.Håkansson,
and
J.R.Winther
(2007).
Structure of glutaredoxin Grx1p C30S mutant from yeast.
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| |
Acta Crystallogr D Biol Crystallogr,
63,
288-294.
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PDB codes:
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M.Schelhaas,
J.Malmström,
L.Pelkmans,
J.Haugstetter,
L.Ellgaard,
K.Grünewald,
and
A.Helenius
(2007).
Simian Virus 40 depends on ER protein folding and quality control factors for entry into host cells.
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Cell,
131,
516-529.
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N.Wajih,
S.M.Hutson,
and
R.Wallin
(2007).
Disulfide-dependent protein folding is linked to operation of the vitamin K cycle in the endoplasmic reticulum. A protein disulfide isomerase-VKORC1 redox enzyme complex appears to be responsible for vitamin K1 2,3-epoxide reduction.
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| |
J Biol Chem,
282,
2626-2635.
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T.M.Buck,
C.M.Wright,
and
J.L.Brodsky
(2007).
The activities and function of molecular chaperones in the endoplasmic reticulum.
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Semin Cell Dev Biol,
18,
751-761.
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A.Görlach,
P.Klappa,
and
T.Kietzmann
(2006).
The endoplasmic reticulum: folding, calcium homeostasis, signaling, and redox control.
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Antioxid Redox Signal,
8,
1391-1418.
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C.W.Gruber,
M.Cemazar,
B.Heras,
J.L.Martin,
and
D.J.Craik
(2006).
Protein disulfide isomerase: the structure of oxidative folding.
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Trends Biochem Sci,
31,
455-464.
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G.Kozlov,
P.Maattanen,
J.D.Schrag,
S.Pollock,
M.Cygler,
B.Nagar,
D.Y.Thomas,
and
K.Gehring
(2006).
Crystal structure of the bb' domains of the protein disulfide isomerase ERp57.
|
| |
Structure,
14,
1331-1339.
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|
PDB code:
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H.P.Su,
D.Y.Lin,
and
D.N.Garboczi
(2006).
The structure of G4, the poxvirus disulfide oxidoreductase essential for virus maturation and infectivity.
|
| |
J Virol,
80,
7706-7713.
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PDB code:
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L.W.Ruddock
(2006).
Gaining access to ERp57 function.
|
| |
Structure,
14,
1209-1210.
|
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P.Maattanen,
G.Kozlov,
K.Gehring,
and
D.Y.Thomas
(2006).
ERp57 and PDI: multifunctional protein disulfide isomerases with similar domain architectures but differing substrate-partner associations.
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Biochem Cell Biol,
84,
881-889.
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R.Ladenstein,
and
B.Ren
(2006).
Protein disulfides and protein disulfide oxidoreductases in hyperthermophiles.
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FEBS J,
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
