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3knd

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Revision as of 09:43, 25 December 2014

TPX2:importin-alpha complex

Structural highlights

3knd is a 2 chain structure with sequence from Mus musculus and Xenopus laevis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	importin alpha 2, Kpna2, Rch1 (Mus musculus), TPX2 (Xenopus laevis)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[IMA2_MOUSE] Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. [TPX2A_XENLA] Spindle assembly factor. Required for normal assembly of mitotic spindles. Mediates the binding kif15 and aurka to spindle microtubules. Required for targeting kif15 to microtubule minus ends. Activates aurka by promoting its autophosphorylation and protects the phosphorylated residue against dephosphorylation (By similarity).^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Novel binding of the mitotic regulator TPX2 (target protein for Xenopus kinesin-like protein 2) to importin-alpha.,Giesecke A, Stewart M J Biol Chem. 2010 Jun 4;285(23):17628-35. Epub 2010 Mar 23. PMID:20335181^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wittmann T, Wilm M, Karsenti E, Vernos I. TPX2, A novel xenopus MAP involved in spindle pole organization. J Cell Biol. 2000 Jun 26;149(7):1405-18. PMID:10871281
↑ Eckerdt F, Pascreau G, Phistry M, Lewellyn AL, DePaoli-Roach AA, Maller JL. Phosphorylation of TPX2 by Plx1 enhances activation of Aurora A. Cell Cycle. 2009 Aug;8(15):2413-9. Epub 2009 Aug 22. PMID:19556869
↑ Giesecke A, Stewart M. Novel binding of the mitotic regulator TPX2 (target protein for Xenopus kinesin-like protein 2) to importin-alpha. J Biol Chem. 2010 Jun 4;285(23):17628-35. Epub 2010 Mar 23. PMID:20335181 doi:http://dx.doi.org/10.1074/jbc.M110.102343

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3knd"

@@ Line 7: / Line 7: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3knd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3knd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3knd RCSB], [http://www.ebi.ac.uk/pdbsum/3knd PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/IMA2_MOUSE IMA2_MOUSE]] Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. [[http://www.uniprot.org/uniprot/TPX2A_XENLA TPX2A_XENLA]] Spindle assembly factor. Required for normal assembly of mitotic spindles. Mediates the binding kif15 and aurka to spindle microtubules. Required for targeting kif15 to microtubule minus ends. Activates aurka by promoting its autophosphorylation and protects the phosphorylated residue against dephosphorylation (By similarity).<ref>PMID:10871281</ref> <ref>PMID:19556869</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3knd

From Proteopedia

Revision as of 09:43, 25 December 2014

TPX2:importin-alpha complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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