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PDBsum entry 3knd
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Protein transport
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PDB id
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3knd
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References listed in PDB file
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Key reference
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Title
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Novel binding of the mitotic regulator tpx2 (target protein for xenopus kinesin-Like protein 2) to importin-Alpha.
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Authors
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A.Giesecke,
M.Stewart.
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Ref.
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J Biol Chem, 2010,
285,
17628-17635.
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PubMed id
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Abstract
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Several aspects of mitotic spindle assembly are orchestrated by the Ran GTPase
through its modulation of the interaction between spindle assembly factors and
importin-alpha. One such factor is TPX2 that promotes microtubule assembly in
the vicinity of chromosomes. TPX2 is inhibited when bound to importin-alpha,
which occurs when the latter is bound to importin-beta. The importin-alpha:beta
interaction is disrupted by the high RanGTP concentration near the chromosomes,
releasing TPX2. In more distal regions, where Ran is predominantly GDP-bound,
TPX2 remains bound to importin-alpha and so is inhibited. Here we use a
combination of structural and biochemical methods to define the basis for TPX2
binding to importin-alpha. A 2.2 A resolution crystal structure shows that the
primary nuclear localization signal ((284)KRKH(287)) of TPX2, which has been
shown to be crucial for inhibition, binds to the minor NLS-binding site on
importin-alpha. This atypical interaction pattern was confirmed using
complementary binding studies that employed importin-alpha variants in which
binding to either the major or minor NLS-binding site was impaired, together
with competition assays using the SV40 monopartite NLS that binds primarily to
the major site. The different way in which TPX2 binds to importin-alpha could
account for much of the selectivity necessary during mitosis because this would
reduce the competition for binding to importin-alpha from other NLS-containing
proteins.
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