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| | ==Solution structure of the C-terminal domain of ERCC1 complexed with the C-terminal domain of XPF== | | ==Solution structure of the C-terminal domain of ERCC1 complexed with the C-terminal domain of XPF== |
| - | <StructureSection load='1z00' size='340' side='right'caption='[[1z00]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1z00' size='340' side='right'caption='[[1z00]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1z00]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z00 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z00 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1z00]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z00 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z00 FirstGlance]. <br> |
| - | </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=1z00 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z00 OCA], [https://pdbe.org/1z00 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z00 RCSB], [https://www.ebi.ac.uk/pdbsum/1z00 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z00 ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1z00 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z00 OCA], [https://pdbe.org/1z00 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z00 RCSB], [https://www.ebi.ac.uk/pdbsum/1z00 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z00 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/ERCC1_HUMAN ERCC1_HUMAN]] Defects in ERCC1 are the cause of cerebro-oculo-facio-skeletal syndrome type 4 (COFS4) [MIM:[https://omim.org/entry/610758 610758]]. COFS is a degenerative autosomal recessive disorder of prenatal onset affecting the brain, eye and spinal cord. After birth, it leads to brain atrophy, hypoplasia of the corpus callosum, hypotonia, cataracts, microcornea, optic atrophy, progressive joint contractures and growth failure. Facial dysmorphism is a constant feature. Abnormalities of the skull, eyes, limbs, heart and kidney also occur.<ref>PMID:17273966</ref> [[https://www.uniprot.org/uniprot/XPF_HUMAN XPF_HUMAN]] Defects in ERCC4 are the cause of xeroderma pigmentosum complementation group F (XP-F) [MIM:[https://omim.org/entry/278760 278760]]; also known as xeroderma pigmentosum VI (XP6). XP-F is an autosomal recessive disease characterized by hypersensitivity of the skin to sunlight followed by high incidence of skin cancer and frequent neurologic abnormalities.<ref>PMID:8797827</ref> <ref>PMID:9580660</ref> <ref>PMID:9579555</ref> Defects in ERCC4 are a cause of XFE progeroid syndrome (XFEPS) [MIM:[https://omim.org/entry/610965 610965]]. This syndrome is illustrated by one patient who presented with dwarfism, cachexia and microcephaly.<ref>PMID:17183314</ref>
| + | [https://www.uniprot.org/uniprot/ERCC1_HUMAN ERCC1_HUMAN] Defects in ERCC1 are the cause of cerebro-oculo-facio-skeletal syndrome type 4 (COFS4) [MIM:[https://omim.org/entry/610758 610758]. COFS is a degenerative autosomal recessive disorder of prenatal onset affecting the brain, eye and spinal cord. After birth, it leads to brain atrophy, hypoplasia of the corpus callosum, hypotonia, cataracts, microcornea, optic atrophy, progressive joint contractures and growth failure. Facial dysmorphism is a constant feature. Abnormalities of the skull, eyes, limbs, heart and kidney also occur.<ref>PMID:17273966</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ERCC1_HUMAN ERCC1_HUMAN]] Structure-specific DNA repair endonuclease responsible for the 5'-incision during DNA repair. [[https://www.uniprot.org/uniprot/XPF_HUMAN XPF_HUMAN]] Structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair. Involved in homologous recombination that assists in removing interstrand cross-link.<ref>PMID:19596235</ref>
| + | [https://www.uniprot.org/uniprot/ERCC1_HUMAN ERCC1_HUMAN] Structure-specific DNA repair endonuclease responsible for the 5'-incision during DNA repair. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ab, E]] | + | [[Category: Ab E]] |
| - | [[Category: Boelens, R]] | + | [[Category: Boelens R]] |
| - | [[Category: Das, D]] | + | [[Category: Das D]] |
| - | [[Category: Folkers, G]] | + | [[Category: Folkers G]] |
| - | [[Category: Hoeijmakers, J H.J]] | + | [[Category: Hoeijmakers JHJ]] |
| - | [[Category: Jaspers, N G.J]] | + | [[Category: Jaspers NGJ]] |
| - | [[Category: Kaptein, R]] | + | [[Category: Kaptein R]] |
| - | [[Category: Odijk, H]] | + | [[Category: Odijk H]] |
| - | [[Category: Tripsianes, K]] | + | [[Category: Tripsianes K]] |
| - | [[Category: Helix-hairpin-helix]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Disease
ERCC1_HUMAN Defects in ERCC1 are the cause of cerebro-oculo-facio-skeletal syndrome type 4 (COFS4) [MIM:610758. COFS is a degenerative autosomal recessive disorder of prenatal onset affecting the brain, eye and spinal cord. After birth, it leads to brain atrophy, hypoplasia of the corpus callosum, hypotonia, cataracts, microcornea, optic atrophy, progressive joint contractures and growth failure. Facial dysmorphism is a constant feature. Abnormalities of the skull, eyes, limbs, heart and kidney also occur.[1]
Function
ERCC1_HUMAN Structure-specific DNA repair endonuclease responsible for the 5'-incision during DNA repair.
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
The human ERCC1/XPF complex is a structure-specific endonuclease with defined polarity that participates in multiple DNA repair pathways. We report the heterodimeric structure of the C-terminal domains of both proteins responsible for ERCC1/XPF complex formation. Both domains exhibit the double helix-hairpin-helix motif (HhH)2, and they are related by a pseudo-2-fold symmetry axis. In the XPF domain, the hairpin of the second motif is replaced by a short turn. The ERCC1 domain folds properly only in the presence of the XPF domain, which implies a role for XPF as a scaffold for the folding of ERCC1. The intersubunit interactions are largely hydrophobic in nature. NMR titration data show that only the ERCC1 domain of the ERCC1/XPF complex is involved in DNA binding. On the basis of these findings, we propose a model for the targeting of XPF nuclease via ERCC1-mediated interactions in the context of nucleotide excision repair.
The structure of the human ERCC1/XPF interaction domains reveals a complementary role for the two proteins in nucleotide excision repair.,Tripsianes K, Folkers G, Ab E, Das D, Odijk H, Jaspers NG, Hoeijmakers JH, Kaptein R, Boelens R Structure. 2005 Dec;13(12):1849-58. PMID:16338413[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jaspers NG, Raams A, Silengo MC, Wijgers N, Niedernhofer LJ, Robinson AR, Giglia-Mari G, Hoogstraten D, Kleijer WJ, Hoeijmakers JH, Vermeulen W. First reported patient with human ERCC1 deficiency has cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure. Am J Hum Genet. 2007 Mar;80(3):457-66. Epub 2007 Jan 29. PMID:17273966 doi:S0002-9297(07)60094-9
- ↑ Tripsianes K, Folkers G, Ab E, Das D, Odijk H, Jaspers NG, Hoeijmakers JH, Kaptein R, Boelens R. The structure of the human ERCC1/XPF interaction domains reveals a complementary role for the two proteins in nucleotide excision repair. Structure. 2005 Dec;13(12):1849-58. PMID:16338413 doi:10.1016/j.str.2005.08.014
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