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Contents |
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56 a.a.
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(+ 0 more)
74 a.a.
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57 a.a.
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49 a.a.
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* Residue conservation analysis
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PDB id:
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| Name: |
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Protein binding
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Title:
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Human rabex-5 residues 1-74 in complex with ubiquitin
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Structure:
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Rab guanine nucleotide exchange factor 1. Chain: a, c, e, g, i, k. Fragment: two ubiqutin binding domains, residues 1-74. Synonym: rabex-5, gef 1. Engineered: yes. Ubiquitin. Chain: b, d, f, h, j, l. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Bos taurus. Bovine. Organism_taxid: 9913.
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Biol. unit:
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Dimer (from
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Resolution:
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2.10Å
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R-factor:
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0.198
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R-free:
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0.238
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Authors:
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L.Penengo,M.Mapelli,A.G.Murachelli,S.Confalioneri,L.Magri, A.Musacchio,P.P.Di Fiore,S.Polo,T.R.Schneider
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Key ref:
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L.Penengo
et al.
(2006).
Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin.
Cell,
124,
1183-1195.
PubMed id:
DOI:
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Date:
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25-Nov-05
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Release date:
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15-Feb-06
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PROCHECK
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Headers
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References
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Q9UJ41
(RABX5_HUMAN) -
Rab5 GDP/GTP exchange factor from Homo sapiens
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Seq:
Struc:
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491 a.a.
56 a.a.
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P0CH28
(UBC_BOVIN) -
Polyubiquitin-C from Bos taurus
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Seq:
Struc:
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690 a.a.
74 a.a.
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Enzyme class:
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Chains A, B, C, D, E, F, G, H, I, J, K, L:
E.C.?
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DOI no:
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Cell
124:1183-1195
(2006)
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PubMed id:
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Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin.
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L.Penengo,
M.Mapelli,
A.G.Murachelli,
S.Confalonieri,
L.Magri,
A.Musacchio,
P.P.Di Fiore,
S.Polo,
T.R.Schneider.
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ABSTRACT
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The interaction between ubiquitinated proteins and intracellular proteins
harboring ubiquitin binding domains (UBDs) is critical to a multitude of
cellular processes. Here, we report that Rabex-5, a guanine nucleotide exchange
factor for Rab5, binds to Ub through two independent UBDs. These UBDs determine
a number of properties of Rabex-5, including its coupled monoubiquitination and
interaction in vivo with ubiquitinated EGFRs. Structural and biochemical
characterization of the UBDs of Rabex-5 revealed that one of them (MIU, motif
interacting with ubiquitin) binds to Ub with modes superimposable to those of
the UIM (ubiquitin-interacting motif):Ub interaction, although in the opposite
orientation. The other UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to
a surface of Ub centered on Asp58(Ub) and distinct from the
"canonical" Ile44(Ub)-based surface. The two binding surfaces allow Ub
to interact simultaneously with different UBDs, thus opening new perspectives in
Ub-mediated signaling.
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Selected figure(s)
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Figure 3.
Figure 3. Overview of the Structure
(A) Secondary
structure diagram (left) and surface representation (right) of
two molecules of RUZ-MIU (yellow and orange) in complex with two
molecules of Ub (light green and dark green). The Zn^2+ ions of
Rabex-5[2–74] are drawn as orange spheres.
(B)
Superposition of two molecules of RUZ-MIU, orange and yellow.
Residues 40–64[Rbx] are shown as a helix, while for residues
17–39[Rbx] the backbone trace is indicated by a tube; Zn^2+
ions are drawn as spheres.
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Figure 5.
Figure 5. The MIU:Ub Complex Resembles the UIM:Ub Complex
(A) Structures of the Rabex-5-MIU:Ub (yellow and green) and
the Vps27-UIM:Ub (red and green) complexes.
(B) 2F[obs] −
1F[calc] difference electron density contoured at the 1σ level
around residue Ala58[Rbx] (yellow) and residues Ile44[Ub] and
Val70[Ub] (green).
(C) Interactions between Ub (green) and
MIU (yellow). Hydrogen bonds and salt bridges are indicated by
dashed black lines.
(D) Ub binding residues of the MIU of
Rabex-5 (yellow) and of the UIM of Vps27 (red). Models of the
RZF-MIU:Ub complex and the Vps27-UIM:Ub complex (Swanson et al.,
2003) were superimposed based on residues 5–70 of the Ub
molecules. Side chains involved in interaction between MIU
(yellow)/UIM (red) and Ub are shown in stick representation.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2006,
124,
1183-1195)
copyright 2006.
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Figures were
selected
by the author.
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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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|
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D.A.Tumbarello,
B.J.Waxse,
S.D.Arden,
N.A.Bright,
J.Kendrick-Jones,
and
F.Buss
(2012).
Autophagy receptors link myosin VI to autophagosomes to mediate Tom1-dependent autophagosome maturation and fusion with the lysosome.
|
| |
Nat Cell Biol,
14,
1024-1035.
|
|
|
|
|
|
|
L.Feng,
and
J.Chen
(2012).
The E3 ligase RNF8 regulates KU80 removal and NHEJ repair.
|
| |
Nat Struct Mol Biol,
19,
201-206.
|
|
|
|
|
|
|
N.V.Dimova,
N.A.Hathaway,
B.H.Lee,
D.S.Kirkpatrick,
M.L.Berkowitz,
S.P.Gygi,
D.Finley,
and
R.W.King
(2012).
APC/C-mediated multiple monoubiquitylation provides an alternative degradation signal for cyclin B1.
|
| |
Nat Cell Biol,
14,
168-176.
|
|
|
|
|
|
|
A.Plechanovová,
E.G.Jaffray,
S.A.McMahon,
K.A.Johnson,
I.Navrátilová,
J.H.Naismith,
and
R.T.Hay
(2011).
Mechanism of ubiquitylation by dimeric RING ligase RNF4.
|
| |
Nat Struct Mol Biol,
18,
1052-1059.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
E.Argenzio,
T.Bange,
B.Oldrini,
F.Bianchi,
R.Peesari,
S.Mari,
P.P.Di Fiore,
M.Mann,
and
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Proteomic snapshot of the EGF-induced ubiquitin network.
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| |
Mol Syst Biol,
7,
462.
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|
|
|
|
|
J.H.Hurley,
and
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(2011).
Molecular mechanisms of ubiquitin-dependent membrane traffic.
|
| |
Annu Rev Biophys,
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|
|
M.Kang,
M.Fokar,
H.Abdelmageed,
and
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(2011).
Arabidopsis SAP5 functions as a positive regulator of stress responses and exhibits E3 ubiquitin ligase activity.
|
| |
Plant Mol Biol,
75,
451-466.
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|
|
|
|
|
|
P.La Rosa,
M.Marino And,
and
F.Acconcia
(2011).
17β-estradiol regulates estrogen receptor α monoubiquitination.
|
| |
IUBMB Life,
63,
49-53.
|
|
|
|
|
|
|
R.M.Blundred,
and
G.S.Stewart
(2011).
DNA double-strand break repair, immunodeficiency and the RIDDLE syndrome.
|
| |
Expert Rev Clin Immunol,
7,
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|
|
|
|
|
|
|
A.X.Song,
C.J.Zhou,
Y.Peng,
X.C.Gao,
Z.R.Zhou,
Q.S.Fu,
J.Hong,
D.H.Lin,
and
H.Y.Hu
(2010).
Structural transformation of the tandem ubiquitin-interacting motifs in ataxin-3 and their cooperative interactions with ubiquitin chains.
|
| |
PLoS One,
5,
e13202.
|
|
|
|
|
|
|
I.Bosanac,
I.E.Wertz,
B.Pan,
C.Yu,
S.Kusam,
C.Lam,
L.Phu,
Q.Phung,
B.Maurer,
D.Arnott,
D.S.Kirkpatrick,
V.M.Dixit,
and
S.G.Hymowitz
(2010).
Ubiquitin binding to A20 ZnF4 is required for modulation of NF-κB signaling.
|
| |
Mol Cell,
40,
548-557.
|
|
|
PDB codes:
|
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|
|
|
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|
|
I.E.Wertz,
and
V.M.Dixit
(2010).
Regulation of death receptor signaling by the ubiquitin system.
|
| |
Cell Death Differ,
17,
14-24.
|
|
|
|
|
|
|
K.Tashiro,
H.Konishi,
H.Nabeshi,
E.Yamauchi,
and
H.Taniguchi
(2010).
[New functional proteins identified by proteomic analysis in the epidermal growth factor receptor-mediated signaling pathway and application for practical use].
|
| |
Yakugaku Zasshi,
130,
471-477.
|
|
|
|
|
|
|
L.Xu,
V.Lubkov,
L.J.Taylor,
and
D.Bar-Sagi
(2010).
Feedback regulation of Ras signaling by Rabex-5-mediated ubiquitination.
|
| |
Curr Biol,
20,
1372-1377.
|
|
|
|
|
|
|
M.G.Bomar,
S.D'Souza,
M.Bienko,
I.Dikic,
G.C.Walker,
and
P.Zhou
(2010).
Unconventional ubiquitin recognition by the ubiquitin-binding motif within the Y family DNA polymerases iota and Rev1.
|
| |
Mol Cell,
37,
408-417.
|
|
|
PDB code:
|
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|
|
|
|
|
|
S.G.Hymowitz,
and
I.E.Wertz
(2010).
A20: from ubiquitin editing to tumour suppression.
|
| |
Nat Rev Cancer,
10,
332-341.
|
|
|
|
|
|
|
A.Galvis,
V.Balmaceda,
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A.Conde,
Z.Villasana,
M.W.Fornes,
and
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(2009).
Inhibition of early endosome fusion by Rab5-binding defective Ras interference 1 mutants.
|
| |
Arch Biochem Biophys,
482,
83-95.
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|
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|
|
|
C.Doil,
N.Mailand,
S.Bekker-Jensen,
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J.Ellenberg,
S.Panier,
D.Durocher,
J.Bartek,
J.Lukas,
and
C.Lukas
(2009).
RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins.
|
| |
Cell,
136,
435-446.
|
|
|
|
|
|
|
C.Francavilla,
P.Cattaneo,
V.Berezin,
E.Bock,
D.Ami,
A.de Marco,
G.Christofori,
and
U.Cavallaro
(2009).
The binding of NCAM to FGFR1 induces a specific cellular response mediated by receptor trafficking.
|
| |
J Cell Biol,
187,
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|
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|
|
E.Laplantine,
E.Fontan,
J.Chiaravalli,
T.Lopez,
G.Lakisic,
M.Véron,
F.Agou,
and
A.Israël
(2009).
NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domain.
|
| |
EMBO J,
28,
2885-2895.
|
|
|
|
|
|
|
G.S.Stewart,
S.Panier,
K.Townsend,
A.K.Al-Hakim,
N.K.Kolas,
E.S.Miller,
S.Nakada,
J.Ylanko,
S.Olivarius,
M.Mendez,
C.Oldreive,
J.Wildenhain,
A.Tagliaferro,
L.Pelletier,
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A.Durandy,
P.J.Byrd,
T.Stankovic,
A.M.Taylor,
and
D.Durocher
(2009).
The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage.
|
| |
Cell,
136,
420-434.
|
|
|
|
|
|
|
H.B.Kamadurai,
J.Souphron,
D.C.Scott,
D.M.Duda,
D.J.Miller,
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R.C.Piper,
and
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(2009).
Insights into ubiquitin transfer cascades from a structure of a UbcH5B approximately ubiquitin-HECT(NEDD4L) complex.
|
| |
Mol Cell,
36,
1095-1102.
|
|
|
PDB codes:
|
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|
|
|
|
|
I.Dikic,
S.Wakatsuki,
and
K.J.Walters
(2009).
Ubiquitin-binding domains - from structures to functions.
|
| |
Nat Rev Mol Cell Biol,
10,
659-671.
|
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|
|
|
|
|
J.M.Bui,
J.Gsponer,
M.Vendruscolo,
and
C.M.Dobson
(2009).
Analysis of sub-tauc and supra-tauc motions in protein Gbeta1 using molecular dynamics simulations.
|
| |
Biophys J,
97,
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|
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M.S.Huen,
L.Y.Lu,
L.Ye,
Y.Dou,
M.Ljungman,
J.Chen,
and
X.Yu
(2009).
Histone ubiquitination associates with BRCA1-dependent DNA damage response.
|
| |
Mol Cell Biol,
29,
849-860.
|
|
|
|
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|
|
Q.S.Fu,
C.J.Zhou,
H.C.Gao,
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J.Hong,
W.M.Yao,
A.X.Song,
D.H.Lin,
and
H.Y.Hu
(2009).
Structural Basis for Ubiquitin Recognition by a Novel Domain from Human Phospholipase A2-activating Protein.
|
| |
J Biol Chem,
284,
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|
|
|
PDB codes:
|
|
|
|
|
|
|
|
S.Pinato,
C.Scandiuzzi,
N.Arnaudo,
E.Citterio,
G.Gaudino,
and
L.Penengo
(2009).
RNF168, a new RING finger, MIU-containing protein that modifies chromatin by ubiquitination of histones H2A and H2AX.
|
| |
BMC Mol Biol,
10,
55.
|
|
|
|
|
|
|
T.E.Messick,
and
R.A.Greenberg
(2009).
The ubiquitin landscape at DNA double-strand breaks.
|
| |
J Cell Biol,
187,
319-326.
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|
|
|
|
|
|
Y.Zwang,
and
Y.Yarden
(2009).
Systems biology of growth factor-induced receptor endocytosis.
|
| |
Traffic,
10,
349-363.
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|
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D.Leonard,
A.Hayakawa,
D.Lawe,
D.Lambright,
K.D.Bellve,
C.Standley,
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K.E.Fogarty,
and
S.Corvera
(2008).
Sorting of EGF and transferrin at the plasma membrane and by cargo-specific signaling to EEA1-enriched endosomes.
|
| |
J Cell Sci,
121,
3445-3458.
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G.Langer,
S.X.Cohen,
V.S.Lamzin,
and
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(2008).
Automated macromolecular model building for X-ray crystallography using ARP/wARP version 7.
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| |
Nat Protoc,
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I.E.Wertz,
and
V.M.Dixit
(2008).
Ubiquitin-mediated regulation of TNFR1 signaling.
|
| |
Cytokine Growth Factor Rev,
19,
313-324.
|
|
|
|
|
|
|
N.A.Lakomek,
K.F.Walter,
C.Farès,
O.F.Lange,
B.L.de Groot,
H.Grubmüller,
R.Brüschweiler,
A.Munk,
S.Becker,
J.Meiler,
and
C.Griesinger
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Self-consistent residual dipolar coupling based model-free analysis for the robust determination of nanosecond to microsecond protein dynamics.
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| |
J Biomol NMR,
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O.F.Lange,
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C.Farès,
G.F.Schröder,
K.F.Walter,
S.Becker,
J.Meiler,
H.Grubmüller,
C.Griesinger,
and
B.L.de Groot
(2008).
Recognition dynamics up to microseconds revealed from an RDC-derived ubiquitin ensemble in solution.
|
| |
Science,
320,
1471-1475.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
O.Hitotsumatsu,
R.C.Ahmad,
R.Tavares,
M.Wang,
D.Philpott,
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C.Werts,
and
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The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2-triggered signals.
|
| |
Immunity,
28,
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O.Okhrimenko,
and
I.Jelesarov
(2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
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| |
J Mol Recognit,
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P.Schreiner,
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I.Dikic,
K.J.Walters,
and
M.Groll
(2008).
Ubiquitin docking at the proteasome through a novel pleckstrin-homology domain interaction.
|
| |
Nature,
453,
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|
PDB codes:
|
|
|
|
|
|
|
|
R.Mattera,
and
J.S.Bonifacino
(2008).
Ubiquitin binding and conjugation regulate the recruitment of Rabex-5 to early endosomes.
|
| |
EMBO J,
27,
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(2008).
Conserved themes in target recognition by the PAH1 and PAH2 domains of the Sin3 transcriptional corepressor.
|
| |
J Mol Biol,
375,
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|
|
PDB codes:
|
|
|
|
|
|
|
|
T.E.Messick,
N.S.Russell,
A.J.Iwata,
K.L.Sarachan,
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K.D.Wilkinson,
and
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(2008).
Structural basis for ubiquitin recognition by the Otu1 ovarian tumor domain protein.
|
| |
J Biol Chem,
283,
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|
|
PDB codes:
|
|
|
|
|
|
|
|
V.Kanneganti,
and
A.K.Gupta
(2008).
Overexpression of OsiSAP8, a member of stress associated protein (SAP) gene family of rice confers tolerance to salt, drought and cold stress in transgenic tobacco and rice.
|
| |
Plant Mol Biol,
66,
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|
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|
Y.Li,
L.Zheng,
F.Corke,
C.Smith,
and
M.W.Bevan
(2008).
Control of final seed and organ size by the DA1 gene family in Arabidopsis thaliana.
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| |
Genes Dev,
22,
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|
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and
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(2007).
Ubiquitin-mediated activation of TAK1 and IKK.
|
| |
Oncogene,
26,
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|
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|
A.Delprato,
and
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(2007).
Structural basis for Rab GTPase activation by VPS9 domain exchange factors.
|
| |
Nat Struct Mol Biol,
14,
406-412.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
B.T.Dye,
and
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PDB code:
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PDB code:
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M.T.Pai,
S.R.Tzeng,
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J Mol Biol,
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PDB code:
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N.B.de la Cruz,
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PDB code:
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P.Peschard,
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PDB codes:
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PDB codes:
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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
code is
shown on the right.
|
| |
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