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PDBsum entry 2ot8
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Transport protein
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PDB id
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2ot8
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References listed in PDB file
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Key reference
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Title
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Structure-Based design of a pathway-Specific nuclear import inhibitor.
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Authors
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A.E.Cansizoglu,
B.J.Lee,
Z.C.Zhang,
B.M.Fontoura,
Y.M.Chook.
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Ref.
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Nat Struct Biol, 2007,
14,
452-454.
[DOI no: ]
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PubMed id
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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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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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