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* Residue conservation analysis
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PDB id:
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Transport protein
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Title:
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Karyopherin beta2/transportin-hnrnpm nls complex
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Structure:
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Transportin-1. Chain: a, b. Synonym: importin beta-2, karyopherin beta-2, m9 region interaction protein, mip. Engineered: yes. Heterogeneous nuclear ribonucleoprotein m. Chain: c, d. Fragment: hnrnpm nls fragment (residues 41-70). Synonym: hnrnp m.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: tnpo1, kpnb2, mip1, trn. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: hnrpm.
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Resolution:
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3.10Å
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R-factor:
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0.255
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R-free:
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0.290
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Authors:
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A.E.Cansizoglu,Y.M.Chook
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Key ref:
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A.E.Cansizoglu
et al.
(2007).
Structure-based design of a pathway-specific nuclear import inhibitor.
Nat Struct Biol,
14,
452-454.
PubMed id:
DOI:
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Date:
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07-Feb-07
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Release date:
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10-Apr-07
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PROCHECK
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Headers
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References
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Q92973
(TNPO1_HUMAN) -
Transportin-1 from Homo sapiens
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Seq:
Struc:
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898 a.a.
824 a.a.
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DOI no:
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Nat Struct Biol
14:452-454
(2007)
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PubMed id:
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Structure-based design of a pathway-specific nuclear import inhibitor.
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A.E.Cansizoglu,
B.J.Lee,
Z.C.Zhang,
B.M.Fontoura,
Y.M.Chook.
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ABSTRACT
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Kapbeta2 (also called transportin) recognizes PY nuclear localization signal
(NLS), a new class of NLS with a R/H/Kx((2-5))PY motif. Here we show that
Kapbeta2 complexes containing hydrophobic and basic PY-NLSs, as classified by
the composition of an additional N-terminal motif, converge in structure only at
consensus motifs, which explains ligand diversity. On the basis of these data
and complementary biochemical analyses, we designed a Kapbeta2-specific nuclear
import inhibitor, M9M.
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Selected figure(s)
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Figure 1.
(a) Ribbon model of Kap  2
(pink), hnRNP M NLS (magenta) and the 2.5  F[o]
– F[c] map (blue). (b) NLSs of hnRNP M (magenta) and hnRNP A1
(2H4M; blue) upon superposition of Kap 2
residues 435–780. Regions of structural similarity are
highlighted in yellow. Structurally aligned NLS sequences, C
 –C
distances
and inhibitor M9M sequence are shown. (c) Loss of Kap 2-binding
energy in alanine mutants of hnRNP A1 (ref.
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Figure 2.
(a–c) Coomassie-stained gels of (a) glutathione
S-transferase (GST) fusions of hnRNP A1 NLS, hnRNP M NLS and M9M
bound to Kap 2
and then dissociated by 0.3–1.6  M
RanGTP; (b) GST–hnRNP A1 NLS bound to Kap 2
in the presence of buffer, maltose-binding protein (MBP)–hnRNP
A1 NLS, MBP–hnRNP M NLS or MBP-M9M; (c) interactions of
GST-Kap 1
with Kap ,
Kap in
the presence of importin- –binding
(IBB) domain of Kap ,
M9M or Kap
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2007,
14,
452-454)
copyright 2007.
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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.Heo
(2011).
Redox control of GTPases: from molecular mechanisms to functional significance in health and disease.
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Antioxid Redox Signal,
14,
689-724.
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L.Gu,
T.Tsuji,
M.A.Jarboui,
G.P.Yeo,
N.Sheehy,
W.W.Hall,
and
V.W.Gautier
(2011).
Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: novel insights into the regulation of Rev nuclear import.
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Retrovirology,
8,
17.
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M.Grünwald,
and
F.Bono
(2011).
Structure of Importin13-Ubc9 complex: nuclear import and release of a key regulator of sumoylation.
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EMBO J,
30,
427-438.
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PDB code:
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R.P.Leemann-Zakaryan,
S.Pahlich,
D.Grossenbacher,
and
H.Gehring
(2011).
Tyrosine Phosphorylation in the C-Terminal Nuclear Localization and Retention Signal (C-NLS) of the EWS Protein.
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Sarcoma,
2011,
218483.
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Y.Kino,
C.Washizu,
E.Aquilanti,
M.Okuno,
M.Kurosawa,
M.Yamada,
H.Doi,
and
N.Nukina
(2011).
Intracellular localization and splicing regulation of FUS/TLS are variably affected by amyotrophic lateral sclerosis-linked mutations.
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Nucleic Acids Res,
39,
2781-2798.
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D.Dormann,
R.Rodde,
D.Edbauer,
E.Bentmann,
I.Fischer,
A.Hruscha,
M.E.Than,
I.R.Mackenzie,
A.Capell,
B.Schmid,
M.Neumann,
and
C.Haass
(2010).
ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import.
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EMBO J,
29,
2841-2857.
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R.Pawłowski,
E.K.Rajakylä,
M.K.Vartiainen,
and
R.Treisman
(2010).
An actin-regulated importin α/β-dependent extended bipartite NLS directs nuclear import of MRTF-A.
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EMBO J,
29,
3448-3458.
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C.K.Lau,
V.A.Delmar,
R.C.Chan,
Q.Phung,
C.Bernis,
B.Fichtman,
B.A.Rasala,
and
D.J.Forbes
(2009).
Transportin regulates major mitotic assembly events: from spindle to nuclear pore assembly.
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Mol Biol Cell,
20,
4043-4058.
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X.Dong,
A.Biswas,
K.E.Süel,
L.K.Jackson,
R.Martinez,
H.Gu,
and
Y.M.Chook
(2009).
Structural basis for leucine-rich nuclear export signal recognition by CRM1.
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Nature,
458,
1136-1141.
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PDB code:
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K.E.Süel,
H.Gu,
and
Y.M.Chook
(2008).
Modular organization and combinatorial energetics of proline-tyrosine nuclear localization signals.
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PLoS Biol,
6,
e137.
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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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Links
