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| | ==Solution structure of a ERCC1-XPA heterodimer== | | ==Solution structure of a ERCC1-XPA heterodimer== |
| - | <StructureSection load='2jnw' size='340' side='right'caption='[[2jnw]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2jnw' size='340' side='right'caption='[[2jnw]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2jnw]] 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=2JNW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JNW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2jnw]] 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=2JNW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JNW FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2a1i|2a1i]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERCC1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2jnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jnw OCA], [https://pdbe.org/2jnw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jnw RCSB], [https://www.ebi.ac.uk/pdbsum/2jnw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jnw ProSAT]</span></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=2jnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jnw OCA], [https://pdbe.org/2jnw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jnw RCSB], [https://www.ebi.ac.uk/pdbsum/2jnw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jnw 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/XPA_HUMAN XPA_HUMAN]] Defects in XPA are a cause of xeroderma pigmentosum complementation group A (XP-A) [MIM:[https://omim.org/entry/278700 278700]]; also known as xeroderma pigmentosum type 1 (XP1). XP-A is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. Group A patients show the most severe skin symptoms and progressive neurological disorders.<ref>PMID:1339397</ref> <ref>PMID:1372103</ref> <ref>PMID:9671271</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/XPA_HUMAN XPA_HUMAN]] Involved in DNA excision repair. Initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. Required for UV-induced CHEK1 phosphorylation and the recruitment of CEP164 to cyclobutane pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation.<ref>PMID:19197159</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: Ivanov, D]] | + | [[Category: Ivanov D]] |
| - | [[Category: Orelli, B]] | + | [[Category: Orelli B]] |
| - | [[Category: Scharer, O D]] | + | [[Category: Scharer OD]] |
| - | [[Category: Staresincic, L]] | + | [[Category: Staresincic L]] |
| - | [[Category: Tsodikov, O V]] | + | [[Category: Tsodikov OV]] |
| - | [[Category: Wagner, G]] | + | [[Category: Wagner G]] |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Ercc1]]
| + | |
| - | [[Category: Ner]]
| + | |
| - | [[Category: Recruitment]]
| + | |
| - | [[Category: Xpa]]
| + | |
| 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 nucleotide excision repair (NER) pathway corrects DNA damage caused by sunlight, environmental mutagens and certain antitumor agents. This multistep DNA repair reaction operates by the sequential assembly of protein factors at sites of DNA damage. The efficient recognition of DNA damage and its repair are orchestrated by specific protein-protein and protein-DNA interactions within NER complexes. We have investigated an essential protein-protein interaction of the NER pathway, the binding of the XPA protein to the ERCC1 subunit of the repair endonuclease ERCC1-XPF. The structure of ERCC1 in complex with an XPA peptide shows that only a small region of XPA interacts with ERCC1 to form a stable complex exhibiting submicromolar binding affinity. However, this XPA peptide is a potent inhibitor of NER activity in a cell-free assay, blocking the excision of a cisplatin adduct from DNA. The structure of the peptide inhibitor bound to its target site reveals a binding interface that is amenable to the development of small molecule peptidomimetics that could be used to modulate NER repair activities in vivo.
Structural basis for the recruitment of ERCC1-XPF to nucleotide excision repair complexes by XPA.,Tsodikov OV, Ivanov D, Orelli B, Staresincic L, Shoshani I, Oberman R, Scharer OD, Wagner G, Ellenberger T EMBO J. 2007 Nov 14;26(22):4768-76. Epub 2007 Oct 18. PMID:17948053[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Tsodikov OV, Ivanov D, Orelli B, Staresincic L, Shoshani I, Oberman R, Scharer OD, Wagner G, Ellenberger T. Structural basis for the recruitment of ERCC1-XPF to nucleotide excision repair complexes by XPA. EMBO J. 2007 Nov 14;26(22):4768-76. Epub 2007 Oct 18. PMID:17948053
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