|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal Structure of the Central Domain of Human ERCC1== | | ==Crystal Structure of the Central Domain of Human ERCC1== |
| - | <StructureSection load='2a1i' size='340' side='right' caption='[[2a1i]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='2a1i' size='340' side='right'caption='[[2a1i]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2a1i]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A1I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2A1I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2a1i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A1I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A1I FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERCC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a1i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a1i OCA], [http://pdbe.org/2a1i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2a1i RCSB], [http://www.ebi.ac.uk/pdbsum/2a1i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2a1i 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=2a1i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a1i OCA], [https://pdbe.org/2a1i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a1i RCSB], [https://www.ebi.ac.uk/pdbsum/2a1i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a1i ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ERCC1_HUMAN ERCC1_HUMAN]] Defects in ERCC1 are the cause of cerebro-oculo-facio-skeletal syndrome type 4 (COFS4) [MIM:[http://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/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 == |
| - | [[http://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/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]] |
| Line 36: |
Line 36: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Ellenberger, T]] | | [[Category: Ellenberger, T]] |
| | [[Category: Enzlin, J H]] | | [[Category: Enzlin, J H]] |
| 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
Human XPF-ERCC1 is a DNA endonuclease that incises a damaged DNA strand on the 5' side of a lesion during nucleotide excision repair and has additional role(s) in homologous recombination and DNA interstrand crosslink repair. We show that a truncated form of XPF lacking the N-terminal helicase-like domain in complex with ERCC1 exhibits a structure-specific endonuclease activity with similar specificity to that of full-length XPF-ERCC1. Two domains of ERCC1, a central domain and a C-terminal tandem helix-hairpin-helix (HhH2) dimerization domain, bind to ssDNA. The central domain of ERCC1 binds ssDNA/dsDNA junctions with a defined polarity, preferring a 5' single-stranded overhang. The XPF-ERCC1 HhH2 domain heterodimer contains two independent ssDNA-binding surfaces, which are revealed by a crystal structure of the protein complex. A crystal structure of the central domain of ERCC1 shows its fold is strikingly similar to that of the nuclease domains of the archaeal Mus81/XPF homologs, despite very low sequence homology. A groove lined with basic and aromatic residues on the surface of ERCC1 has apparently been adapted to interact with ssDNA. On the basis of these crystallographic and biochemical studies, we propose a model in which XPF-ERCC1 recognizes a branched DNA substrate by binding the two ssDNA arms with the two HhH2 domains of XPF and ERCC1 and by binding the 5'-ssDNA arm with the central domain of ERCC1.
Crystal structure and DNA binding functions of ERCC1, a subunit of the DNA structure-specific endonuclease XPF-ERCC1.,Tsodikov OV, Enzlin JH, Scharer OD, Ellenberger T Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11236-41. Epub 2005 Aug 2. PMID:16076955[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, Enzlin JH, Scharer OD, Ellenberger T. Crystal structure and DNA binding functions of ERCC1, a subunit of the DNA structure-specific endonuclease XPF-ERCC1. Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11236-41. Epub 2005 Aug 2. PMID:16076955
|
