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4mz5

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Revision as of 17:11, 4 August 2016

Structure of importin-alpha: dUTPase NLS complex

Structural highlights

4mz5 is a 3 chain structure with sequence from Lk3 transgenic mice. This structure supersedes the now removed PDB entry 4fdr. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1elj, 3ukw, 4mz6
Gene:	Kpna2, Rch1 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DUT_HUMAN] This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.^[1] [IMA1_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.

Publication Abstract from PubMed

Phosphorylation adjacent to nuclear localization signals (NLSs) is involved in the regulation of nucleocytoplasmic transport. The nuclear isoform of human dUTPase, an enzyme that is essential for genomic integrity, has been shown to be phosphorylated on a serine residue (Ser11) in the vicinity of its nuclear localization signal; however, the effect of this phosphorylation is not yet known. To investigate this issue, an integrated set of structural, molecular and cell biological methods were employed. It is shown that NLS-adjacent phosphorylation of dUTPase occurs during the M phase of the cell cycle. Comparison of the cellular distribution of wild-type dUTPase with those of hyperphosphorylation- and hypophosphorylation-mimicking mutants suggests that phosphorylation at Ser11 leads to the exclusion of dUTPase from the nucleus. Isothermal titration microcalorimetry and additional independent biophysical techniques show that the interaction between dUTPase and importin-alpha, the karyopherin molecule responsible for `classical' NLS binding, is weakened significantly in the case of the S11E hyperphosphorylation-mimicking mutant. The structures of the importin-alpha-wild-type and the importin-alpha-hyperphosphorylation-mimicking dUTPase NLS complexes provide structural insights into the molecular details of this regulation. The data indicate that the post-translational modification of dUTPase during the cell cycle may modulate the nuclear availability of this enzyme.

Phosphorylation adjacent to the nuclear localization signal of human dUTPase abolishes nuclear import: structural and mechanistic insights.,Rona G, Marfori M, Borsos M, Scheer I, Takacs E, Toth J, Babos F, Magyar A, Erdei A, Bozoky Z, Buday L, Kobe B, Vertessy BG Acta Crystallogr D Biol Crystallogr. 2013 Dec;69(Pt 12):2495-505. doi:, 10.1107/S0907444913023354. Epub 2013 Nov 19. PMID:24311590^[2]

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

References

↑ Mol CD, Harris JM, McIntosh EM, Tainer JA. Human dUTP pyrophosphatase: uracil recognition by a beta hairpin and active sites formed by three separate subunits. Structure. 1996 Sep 15;4(9):1077-92. PMID:8805593
↑ Rona G, Marfori M, Borsos M, Scheer I, Takacs E, Toth J, Babos F, Magyar A, Erdei A, Bozoky Z, Buday L, Kobe B, Vertessy BG. Phosphorylation adjacent to the nuclear localization signal of human dUTPase abolishes nuclear import: structural and mechanistic insights. Acta Crystallogr D Biol Crystallogr. 2013 Dec;69(Pt 12):2495-505. doi:, 10.1107/S0907444913023354. Epub 2013 Nov 19. PMID:24311590 doi:http://dx.doi.org/10.1107/S0907444913023354

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4mz5"

@@ Line 1: / Line 1: @@
 ==Structure of importin-alpha: dUTPase NLS complex==
 <StructureSection load='4mz5' size='340' side='right' caption='[[4mz5]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1elj|1elj]], [[3ukw|3ukw]], [[4mz6|4mz6]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Kpna2, Rch1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
-<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=4mz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mz5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mz5 RCSB], [http://www.ebi.ac.uk/pdbsum/4mz5 PDBsum]</span></td></tr>
+<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=4mz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mz5 OCA], [http://pdbe.org/4mz5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mz5 RCSB], [http://www.ebi.ac.uk/pdbsum/4mz5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mz5 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4mz5" style="background-color:#fffaf0;"></div>
 ==See Also==

4mz5

From Proteopedia

Revision as of 17:11, 4 August 2016

Structure of importin-alpha: dUTPase NLS complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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