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| | <StructureSection load='5ekf' size='340' side='right'caption='[[5ekf]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='5ekf' size='340' side='right'caption='[[5ekf]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ekf]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EKF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EKF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ekf]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EKF FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ekg|5ekg]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=5ekf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ekf OCA], [https://pdbe.org/5ekf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ekf RCSB], [https://www.ebi.ac.uk/pdbsum/5ekf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ekf ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ekf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ekf OCA], [http://pdbe.org/5ekf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ekf RCSB], [http://www.ebi.ac.uk/pdbsum/5ekf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ekf ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ERCC5_HUMAN ERCC5_HUMAN]] Xeroderma pigmentosum complementation group G;COFS syndrome. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/ERCC5_HUMAN ERCC5_HUMAN] Xeroderma pigmentosum complementation group G;COFS syndrome. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ERCC5_HUMAN ERCC5_HUMAN]] Single-stranded structure-specific DNA endonuclease involved in DNA excision repair. Makes the 3'incision in DNA nucleotide excision repair (NER). Acts as a cofactor for a DNA glycosylase that removes oxidized pyrimidines from DNA. May also be involved in transcription-coupled repair of this kind of damage, in transcription by RNA polymerase II, and perhaps in other processes too. [[http://www.uniprot.org/uniprot/IMA1_MOUSE 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. | + | [https://www.uniprot.org/uniprot/ERCC5_HUMAN ERCC5_HUMAN] Single-stranded structure-specific DNA endonuclease involved in DNA excision repair. Makes the 3'incision in DNA nucleotide excision repair (NER). Acts as a cofactor for a DNA glycosylase that removes oxidized pyrimidines from DNA. May also be involved in transcription-coupled repair of this kind of damage, in transcription by RNA polymerase II, and perhaps in other processes too. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
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| - | Xeroderma pigmentosum type G (XPG) proteins are involved in DNA lesion recognition and promotion of nucleotide excision repair (NER). Specific mutations in these proteins may lead to Cockayne syndrome, in which the patients may display severe developmental retardation and neurological abnormalities. No structural information is available for their spacer region or the C-terminal domain, which are important, respectively, for specific NER activity and substrate specificity, and nuclear translocation. Immunofluorescence studies suggested two specific regions of the XPG C-terminus as potential bipartite nuclear localization sequences, which would be responsible for its translocation to the nucleus by the classical nuclear import pathway mediated by importin-alpha (Impalpha). Thus, in order to test these hypotheses and gain insight into the structural basis for the nuclear import process for the XPG protein, we solved the crystal structures of complexes formed by the Impalpha and peptides corresponding to both putative NLS (nuclear localization signal) sequences (XPG1 and XPG2) and performed isothermal titration calorimetry (ITC) assays to determine their binding affinities. Structural experiments confirm the binding of both NLS peptides to Impalpha but, unexpectedly, they bind to the receptor as monopartite NLSs. The ITC assays demonstrated that XPG1 and XPG2 peptides bind to two separate binding-sites, but with high affinity to the major NLS binding-site of the Impalpha, resembling classical monopartite SV40 TAg NLS. The results lead to insights about what distinguishes monopartite and bipartite NLSs, as well as the differential roles of XPG1 and XPG2 NLSs in the nuclear localization of XPG.
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| - | Structural and calorimetric studies demonstrate that Xeroderma pigmentosum type G (XPG) can be imported to the nucleus by a classical nuclear import pathway via a monopartite NLS sequence.,de Barros AC, Takeda AA, Dreyer TR, Velazquez-Campoy A, Kobe B, Fontes MR J Mol Biol. 2016 Jan 23. pii: S0022-2836(16)00038-3. doi:, 10.1016/j.jmb.2016.01.019. PMID:26812207<ref>PMID:26812207</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5ekf" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Importin 3D structures|Importin 3D structures]] | | *[[Importin 3D structures|Importin 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Barros, A C]] | + | [[Category: Barros AC]] |
| - | [[Category: Fontes, M R.M]] | + | [[Category: Fontes MRM]] |
| - | [[Category: Takeda, A A.S]] | + | [[Category: Takeda AAS]] |
| - | [[Category: Dna repair protein]]
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| - | [[Category: Importin alpha]]
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| - | [[Category: Nuclear import pathway]]
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| - | [[Category: Nucleotide excision repair]]
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| - | [[Category: Protein binding]]
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| - | [[Category: Xpg protein]]
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