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* Residue conservation analysis
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PDB id:
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Protein binding
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Title:
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Ubiquitin recognition by npl4 zinc-fingers
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Structure:
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Homolog of yeast nuclear protein localization 4. Chain: a. Fragment: npl4 nzf domain (residues 580-608). Engineered: yes. Ubiquitin. Chain: b. Engineered: yes
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Source:
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Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: npl4. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Homo sapiens. Human. Organism_taxid: 9606.
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NMR struc:
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20 models
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Authors:
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S.L.Alam,J.Sun,M.Payne,B.D.Welch,B.K.Blake,D.R.Davis,H.H.Meyer, S.D.Emr,W.I.Sundquist
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Key ref:
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S.L.Alam
et al.
(2004).
Ubiquitin interactions of NZF zinc fingers.
EMBO J,
23,
1411-1421.
PubMed id:
DOI:
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Date:
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11-Aug-03
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Release date:
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30-Mar-04
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PROCHECK
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Headers
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References
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Enzyme class:
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Chains A, B:
E.C.?
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DOI no:
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EMBO J
23:1411-1421
(2004)
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PubMed id:
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Ubiquitin interactions of NZF zinc fingers.
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S.L.Alam,
J.Sun,
M.Payne,
B.D.Welch,
B.K.Blake,
D.R.Davis,
H.H.Meyer,
S.D.Emr,
W.I.Sundquist.
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ABSTRACT
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Ubiquitin (Ub) functions in many different biological pathways, where it
typically interacts with proteins that contain modular Ub recognition domains.
One such recognition domain is the Npl4 zinc finger (NZF), a compact
zinc-binding module found in many proteins that function in Ub-dependent
processes. We now report the solution structure of the NZF domain from Npl4 in
complex with Ub. The structure reveals that three key NZF residues (13TF14/M25)
surrounding the zinc coordination site bind the hydrophobic 'Ile44' surface of
Ub. Mutations in the 13TF14/M25 motif inhibit Ub binding, and naturally
occurring NZF domains that lack the motif do not bind Ub. However, substitution
of the 13TF14/M25 motif into the nonbinding NZF domain from RanBP2 creates
Ub-binding activity, demonstrating the versatility of the NZF scaffold. Finally,
NZF mutations that inhibit Ub binding by the NZF domain of Vps36/ESCRT-II also
inhibit sorting of ubiquitylated proteins into the yeast vacuole. Thus, the NZF
is a versatile protein recognition domain that is used to bind ubiquitylated
proteins during vacuolar protein sorting, and probably many other biological
processes.
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Selected figure(s)
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Figure 3.
Figure 3 Npl4 NZF/Ub interaction surfaces. (A) Stereoview of
Npl4 NZF (ribbon) bound to Ub (surface). Ub residue numbers are
shown. (B) Stereoview of Ub (ribbon) bound to Npl4 NZF
(surface). NZF residue numbers are shown. (C) Expanded
stereoview showing the key interface residues (numbered) from
Npl4 NZF (blue) and Ub (red).
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Figure 4.
Figure 4 Transferability of the NZF [13]TF[14]/M[25] Ub-binding
motif. (A) Schematic alignment of the Npl4 and RanBP2 NZF
sequences. Dark blue: highly conserved NZF residues (>50%);
light blue: moderately conserved NZF residues (>20%); yellow:
residues that contact Ub; and green: residues that are both
highly conserved and contact Ub. NZF residue conservation was
defined as in Wang et al (2003). (B) Ub binding by wt (inset)
and mutant RanBP2 (L13T,V14F,A25M) NZF domains. Ub was injected
in triplicate at concentrations of 0 -1500 M
over GST-RanBP2 NZF proteins captured on anti-GST surfaces. Note
that Ub binding by the wt RanBP2 NZF domain (inset) was
negligible, even at 1500 M
Ub. (C) Binding isotherms for the NZF domains of Npl4 (positive
control, black), wt RanBP2 (negative control, purple), RanBP2
(L13T,V14F) (blue), RanBP2 (L13T,V14F,A25M) (green), and RanBP2
(L13T,V14F,A24E,A25M) (red). K[d] values are given in Table II.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2004,
23,
1411-1421)
copyright 2004.
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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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L.Zhang,
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L.Liu,
S.Chen,
and
F.Shao
(2012).
Cysteine methylation disrupts ubiquitin-chain sensing in NF-κB activation.
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Nature,
481,
204-208.
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|
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|
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Y.Kulathu,
and
D.Komander
(2012).
Atypical ubiquitylation - the unexplored world of polyubiquitin beyond Lys48 and Lys63 linkages.
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Nat Rev Mol Cell Biol,
13,
508-523.
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F.Arnesano,
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R.Caliandro,
G.Falini,
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and
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(2011).
Crystallographic analysis of metal-ion binding to human ubiquitin.
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Chemistry,
17,
1569-1578.
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PDB codes:
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J.P.Mackay,
J.Font,
and
D.J.Segal
(2011).
The prospects for designer single-stranded RNA-binding proteins.
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Linear ubiquitin assembly complex negatively regulates RIG-I- and TRIM25-mediated type I interferon induction.
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Mol Cell,
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and
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Regulators of Vps4 ATPase activity at endosomes differentially influence the size and rate of formation of intralumenal vesicles.
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Mol Biol Cell,
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D.Teis,
S.Saksena,
B.L.Judson,
and
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(2010).
ESCRT-II coordinates the assembly of ESCRT-III filaments for cargo sorting and multivesicular body vesicle formation.
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EMBO J,
29,
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J.H.Hurley,
and
P.I.Hanson
(2010).
Membrane budding and scission by the ESCRT machinery: it's all in the neck.
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Nat Rev Mol Cell Biol,
11,
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J.H.Hurley
(2010).
The ESCRT complexes.
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Crit Rev Biochem Mol Biol,
45,
463-487.
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J.R.Mullen,
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Wss1 is a SUMO-dependent isopeptidase that interacts genetically with the Slx5-Slx8 SUMO-targeted ubiquitin ligase.
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Mol Cell Biol,
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3737-3748.
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T.Wollert,
and
J.H.Hurley
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Molecular mechanism of multivesicular body biogenesis by ESCRT complexes.
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Nature,
464,
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D.M.LeMaster,
J.S.Anderson,
and
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Biochemistry,
48,
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F.E.Loughlin,
R.E.Mansfield,
P.M.Vaz,
A.P.McGrath,
S.Setiyaputra,
R.Gamsjaeger,
E.S.Chen,
B.J.Morris,
J.M.Guss,
and
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(2009).
The zinc fingers of the SR-like protein ZRANB2 are single-stranded RNA-binding domains that recognize 5' splice site-like sequences.
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Proc Natl Acad Sci U S A,
106,
5581-5586.
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PDB code:
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F.Mancini,
G.D.Conza,
and
F.Moretti
(2009).
MDM4 (MDMX) and its Transcript Variants.
|
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Curr Genomics,
10,
42-50.
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I.Dikic,
S.Wakatsuki,
and
K.J.Walters
(2009).
Ubiquitin-binding domains - from structures to functions.
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Nat Rev Mol Cell Biol,
10,
659-671.
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J.R.Partridge,
and
T.U.Schwartz
(2009).
Crystallographic and biochemical analysis of the Ran-binding zinc finger domain.
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J Mol Biol,
391,
375-389.
|
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PDB codes:
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S.B.Shields,
A.J.Oestreich,
S.Winistorfer,
D.Nguyen,
J.A.Payne,
D.J.Katzmann,
and
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(2009).
ESCRT ubiquitin-binding domains function cooperatively during MVB cargo sorting.
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| |
J Cell Biol,
185,
213-224.
|
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Y.Kulathu,
M.Akutsu,
A.Bremm,
K.Hofmann,
and
D.Komander
(2009).
Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain.
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Nat Struct Mol Biol,
16,
1328-1330.
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PDB codes:
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Y.Sato,
A.Yoshikawa,
M.Yamashita,
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and
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Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by NZF domains of TAB2 and TAB3.
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28,
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PDB codes:
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Y.Zhang,
and
H.Lu
(2009).
Signaling to p53: ribosomal proteins find their way.
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| |
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16,
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and
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T.Schwarz-Romond,
and
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(2008).
Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains.
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Genes Dev,
22,
528-542.
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I.González,
R.Aparicio,
and
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(2008).
Functional characterization of the dRYBP gene in Drosophila.
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Genetics,
179,
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N.Schrader,
C.Koerner,
K.Koessmeier,
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and
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(2008).
The crystal structure of the Ran-Nup153ZnF2 complex: a general Ran docking site at the nuclear pore complex.
|
| |
Structure,
16,
1116-1125.
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PDB codes:
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N.Tanaka,
M.Kyuuma,
and
K.Sugamura
(2008).
Endosomal sorting complex required for transport proteins in cancer pathogenesis, vesicular transport, and non-endosomal functions.
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Cancer Sci,
99,
1293-1303.
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M.K.Swanton,
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J.A.Lowry,
A.H.Kwan,
J.M.Matthews,
and
J.P.Mackay
(2008).
Structural and biophysical analysis of the DNA binding properties of myelin transcription factor 1.
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J Biol Chem,
283,
5158-5167.
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PDB code:
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T.E.Messick,
N.S.Russell,
A.J.Iwata,
K.L.Sarachan,
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J.R.Shanks,
F.E.Reyes-Turcu,
K.D.Wilkinson,
and
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(2008).
Structural basis for ubiquitin recognition by the Otu1 ovarian tumor domain protein.
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J Biol Chem,
283,
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PDB codes:
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Y.Amemiya,
P.Azmi,
and
A.Seth
(2008).
Autoubiquitination of BCA2 RING E3 ligase regulates its own stability and affects cell migration.
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Mol Cancer Res,
6,
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Y.J.Im,
and
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(2008).
Integrated structural model and membrane targeting mechanism of the human ESCRT-II complex.
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| |
Dev Cell,
14,
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PDB codes:
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D.J.Gill,
H.Teo,
J.Sun,
O.Perisic,
D.B.Veprintsev,
S.D.Emr,
and
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(2007).
Structural insight into the ESCRT-I/-II link and its role in MVB trafficking.
|
| |
EMBO J,
26,
600-612.
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PDB codes:
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D.P.Nickerson,
M.R.Russell,
and
G.Odorizzi
(2007).
A concentric circle model of multivesicular body cargo sorting.
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| |
EMBO Rep,
8,
644-650.
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J.Martin-Serrano
(2007).
The role of ubiquitin in retroviral egress.
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Traffic,
8,
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L.Malerød,
S.Stuffers,
A.Brech,
and
H.Stenmark
(2007).
Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth factor and chemokine receptors destined for lysosomal degradation.
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| |
Traffic,
8,
1617-1629.
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M.G.Bomar,
M.T.Pai,
S.R.Tzeng,
S.S.Li,
and
P.Zhou
(2007).
Structure of the ubiquitin-binding zinc finger domain of human DNA Y-polymerase eta.
|
| |
EMBO Rep,
8,
247-251.
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PDB code:
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M.M.Higa,
S.L.Alam,
W.I.Sundquist,
and
K.S.Ullman
(2007).
Molecular characterization of the Ran-binding zinc finger domain of Nup153.
|
| |
J Biol Chem,
282,
17090-17100.
|
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PDB code:
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M.S.Lindström,
A.Jin,
C.Deisenroth,
G.White Wolf,
and
Y.Zhang
(2007).
Cancer-associated mutations in the MDM2 zinc finger domain disrupt ribosomal protein interaction and attenuate MDM2-induced p53 degradation.
|
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Mol Cell Biol,
27,
1056-1068.
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M.Zhadina,
M.O.McClure,
M.C.Johnson,
and
P.D.Bieniasz
(2007).
Ubiquitin-dependent virus particle budding without viral protein ubiquitination.
|
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Proc Natl Acad Sci U S A,
104,
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R.C.Piper,
and
D.J.Katzmann
(2007).
Biogenesis and function of multivesicular bodies.
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Annu Rev Cell Dev Biol,
23,
519-547.
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R.L.Williams,
and
S.Urbé
(2007).
The emerging shape of the ESCRT machinery.
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Nat Rev Mol Cell Biol,
8,
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V.E.Pye,
F.Beuron,
C.A.Keetch,
C.McKeown,
C.V.Robinson,
H.H.Meyer,
X.Zhang,
and
P.S.Freemont
(2007).
Structural insights into the p97-Ufd1-Npl4 complex.
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Proc Natl Acad Sci U S A,
104,
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S.Elgort,
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M.Dasso,
and
K.S.Ullman
(2006).
Nuclear envelope breakdown is coordinated by both Nup358/RanBP2 and Nup153, two nucleoporins with zinc finger modules.
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Mol Biol Cell,
17,
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|
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C.Boyault,
B.Gilquin,
Y.Zhang,
V.Rybin,
E.Garman,
W.Meyer-Klaucke,
P.Matthias,
C.W.Müller,
and
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(2006).
HDAC6-p97/VCP controlled polyubiquitin chain turnover.
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| |
EMBO J,
25,
3357-3366.
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C.Langelier,
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J.Kaplan,
D.Ward,
and
W.I.Sundquist
(2006).
Human ESCRT-II complex and its role in human immunodeficiency virus type 1 release.
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J Virol,
80,
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J.E.Mullally,
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The ubiquitin binding domain ZnF UBP recognizes the C-terminal diglycine motif of unanchored ubiquitin.
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| |
Cell,
124,
1197-1208.
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PDB codes:
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G.W.Yu,
M.D.Allen,
A.Andreeva,
A.R.Fersht,
and
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Solution structure of the C4 zinc finger domain of HDM2.
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Protein Sci,
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PDB codes:
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H.Teo,
D.J.Gill,
J.Sun,
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D.B.Veprintsev,
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S.D.Emr,
and
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ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes.
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Cell,
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99.
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PDB codes:
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J.H.Hurley,
and
S.D.Emr
(2006).
The ESCRT complexes: structure and mechanism of a membrane-trafficking network.
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Annu Rev Biophys Biomol Struct,
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D.J.Owen,
P.J.Lehner,
and
J.P.Luzio
(2006).
Degradation of endocytosed epidermal growth factor and virally ubiquitinated major histocompatibility complex class I is independent of mammalian ESCRTII.
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| |
J Biol Chem,
281,
5094-5105.
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L.Penengo,
M.Mapelli,
A.G.Murachelli,
S.Confalonieri,
L.Magri,
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P.P.Di Fiore,
S.Polo,
and
T.R.Schneider
(2006).
Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin.
|
| |
Cell,
124,
1183-1195.
|
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|
PDB codes:
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|
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M.R.Russell,
D.P.Nickerson,
and
G.Odorizzi
(2006).
Molecular mechanisms of late endosome morphology, identity and sorting.
|
| |
Curr Opin Cell Biol,
18,
422-428.
|
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|
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M.S.Kostelansky,
J.Sun,
S.Lee,
J.Kim,
R.Ghirlando,
A.Hierro,
S.D.Emr,
and
J.H.Hurley
(2006).
Structural and functional organization of the ESCRT-I trafficking complex.
|
| |
Cell,
125,
113-126.
|
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|
PDB codes:
|
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S.Hirano,
M.Kawasaki,
H.Ura,
R.Kato,
C.Raiborg,
H.Stenmark,
and
S.Wakatsuki
(2006).
Double-sided ubiquitin binding of Hrs-UIM in endosomal protein sorting.
|
| |
Nat Struct Mol Biol,
13,
272-277.
|
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|
PDB code:
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Nat Struct Mol Biol,
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PDB code:
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S.L.Alam,
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Structural basis for ubiquitin recognition by the human ESCRT-II EAP45 GLUE domain.
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Nat Struct Mol Biol,
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PDB code:
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S.Lee,
Y.C.Tsai,
R.Mattera,
W.J.Smith,
M.S.Kostelansky,
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Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5.
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Nat Struct Mol Biol,
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PDB codes:
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T.Chu,
J.Sun,
S.Saksena,
and
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New component of ESCRT-I regulates endosomal sorting complex assembly.
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J Cell Biol,
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Trends Cell Biol,
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Exploring the ESCRTing machinery in eukaryotes.
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Trends Plant Sci,
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Solution structure of the ubiquitin-associated domain of human BMSC-UbP and its complex with ubiquitin.
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Protein Sci,
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PDB codes:
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NMR analysis of protein interactions.
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Structure of the UBA domain of Dsk2p in complex with ubiquitin molecular determinants for ubiquitin recognition.
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Structure,
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PDB code:
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C.Tsui,
A.Raguraj,
and
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Ubiquitin binding site of the ubiquitin E2 variant (UEV) protein Mms2 is required for DNA damage tolerance in the yeast RAD6 pathway.
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J Biol Chem,
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D.T.Huang,
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and
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Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1.
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Mol Cell,
17,
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PDB code:
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G.Prag,
S.Lee,
R.Mattera,
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Structural mechanism for ubiquitinated-cargo recognition by the Golgi-localized, gamma-ear-containing, ADP-ribosylation-factor-binding proteins.
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Proc Natl Acad Sci U S A,
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PDB code:
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S.Sitaraman,
A.Hierro,
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G.Odorizzi,
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(2005).
Structural basis for endosomal targeting by the Bro1 domain.
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Dev Cell,
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PDB code:
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J.Martin-Serrano,
S.W.Eastman,
W.Chung,
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HECT ubiquitin ligases link viral and cellular PPXY motifs to the vacuolar protein-sorting pathway.
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J Cell Biol,
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Small ubiquitin-like modifier (SUMO) recognition of a SUMO binding motif: a reversal of the bound orientation.
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J Biol Chem,
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PDB code:
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L.Hicke,
H.L.Schubert,
and
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Ubiquitin-binding domains.
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Traffic,
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Regulating the regulators: control of protein ubiquitination and ubiquitin-like modifications by extracellular stimuli.
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Mol Cell,
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Molecular mechanism of ubiquitin recognition by GGA3 GAT domain.
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Genes Cells,
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PDB code:
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R.L.Rich,
and
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(2005).
Survey of the year 2004 commercial optical biosensor literature.
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J Mol Recognit,
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A small conserved surface in SUMO is the critical structural determinant of its transcriptional inhibitory properties.
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Mol Cell Biol,
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Delivery of ubiquitinated substrates to protein-unfolding machines.
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Eap45 in mammalian ESCRT-II binds ubiquitin via a phosphoinositide-interacting GLUE domain.
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J Biol Chem,
280,
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Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains.
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J Biol Chem,
280,
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PDB code:
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A.Hierro,
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A.S.Rusnak,
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G.Prag,
S.D.Emr,
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Structure of the ESCRT-II endosomal trafficking complex.
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Nature,
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PDB code:
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A.K.Wernimont,
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Crystal structure of subunit VPS25 of the endosomal trafficking complex ESCRT-II.
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PDB code:
|
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C.M.Pickart,
and
D.Fushman
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Polyubiquitin chains: polymeric protein signals.
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Retrovirus budding.
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Cbl-dependent ubiquitination is required for progression of EGF receptors into clathrin-coated pits.
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Crystal structure of human otubain 2.
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| |
EMBO Rep,
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PDB code:
|
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|
|
|
|
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P.S.Bilodeau,
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The GAT domains of clathrin-associated GGA proteins have two ubiquitin binding motifs.
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J Biol Chem,
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The AAA ATPase p97/VCP interacts with its alternative co-factors, Ufd1-Npl4 and p47, through a common bipartite binding mechanism.
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J Biol Chem,
279,
49609-49616.
|
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|
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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.
|
');
}
}
 |