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[[Image:2a1j.gif|left|200px]]


{{Structure
==Crystal Structure of the Complex between the C-Terminal Domains of Human XPF and ERCC1==
|PDB= 2a1j |SIZE=350|CAPTION= <scene name='initialview01'>2a1j</scene>, resolution 2.70&Aring;
<StructureSection load='2a1j' size='340' side='right'caption='[[2a1j]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=HG:MERCURY (II) ION'>HG</scene>
<table><tr><td colspan='2'>[[2a1j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A1J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A1J FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
|GENE= ERCC4, ERCC11, XPF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), ERCC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
<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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2a1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a1j OCA], [https://pdbe.org/2a1j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a1j RCSB], [https://www.ebi.ac.uk/pdbsum/2a1j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a1j ProSAT]</span></td></tr>
</table>
== Disease ==
[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>
== Function ==
[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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a1/2a1j_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2a1j ConSurf].
<div style="clear:both"></div>


'''Crystal Structure of the Complex between the C-Terminal Domains of Human XPF and ERCC1'''
==See Also==
 
*[[Endonuclease 3D structures|Endonuclease 3D structures]]
 
== References ==
==Overview==
<references/>
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.
__TOC__
 
</StructureSection>
==Disease==
Known diseases associated with this structure: Cerebrooculofacioskeletal syndrome 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=126380 126380]], XFE progeroid syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133520 133520]], Xeroderma pigmentosum, group F OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133520 133520]]
 
==About this Structure==
2A1J is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A1J OCA].
 
==Reference==
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:[http://www.ncbi.nlm.nih.gov/pubmed/16076955 16076955]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Ellenberger, T.]]
[[Category: Ellenberger T]]
[[Category: Enzlin, J H.]]
[[Category: Enzlin JH]]
[[Category: Scharer, O D.]]
[[Category: Scharer OD]]
[[Category: Tsodikov, O V.]]
[[Category: Tsodikov OV]]
[[Category: HG]]
[[Category: dna repair]]
[[Category: endonuclease]]
[[Category: ercc1]]
[[Category: helix-hairpin-helix]]
[[Category: ner]]
[[Category: xeroderma pigmentosum]]
[[Category: xpf]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:44:19 2008''

Latest revision as of 12:10, 14 February 2024

Crystal Structure of the Complex between the C-Terminal Domains of Human XPF and ERCC1Crystal Structure of the Complex between the C-Terminal Domains of Human XPF and ERCC1

Structural highlights

2a1j is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.7Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

XPF_HUMAN Defects in ERCC4 are the cause of xeroderma pigmentosum complementation group F (XP-F) [MIM: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.[1] [2] [3] Defects in ERCC4 are a cause of XFE progeroid syndrome (XFEPS) [MIM:610965. This syndrome is illustrated by one patient who presented with dwarfism, cachexia and microcephaly.[4]

Function

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.[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Sijbers AM, de Laat WL, Ariza RR, Biggerstaff M, Wei YF, Moggs JG, Carter KC, Shell BK, Evans E, de Jong MC, Rademakers S, de Rooij J, Jaspers NG, Hoeijmakers JH, Wood RD. Xeroderma pigmentosum group F caused by a defect in a structure-specific DNA repair endonuclease. Cell. 1996 Sep 6;86(5):811-22. PMID:8797827
  2. ↑ Matsumura Y, Nishigori C, Yagi T, Imamura S, Takebe H. Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms. Hum Mol Genet. 1998 Jun;7(6):969-74. PMID:9580660
  3. ↑ Sijbers AM, van Voorst Vader PC, Snoek JW, Raams A, Jaspers NG, Kleijer WJ. Homozygous R788W point mutation in the XPF gene of a patient with xeroderma pigmentosum and late-onset neurologic disease. J Invest Dermatol. 1998 May;110(5):832-6. PMID:9579555 doi:10.1046/j.1523-1747.1998.00171.x
  4. ↑ Niedernhofer LJ, Garinis GA, Raams A, Lalai AS, Robinson AR, Appeldoorn E, Odijk H, Oostendorp R, Ahmad A, van Leeuwen W, Theil AF, Vermeulen W, van der Horst GT, Meinecke P, Kleijer WJ, Vijg J, Jaspers NG, Hoeijmakers JH. A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature. 2006 Dec 21;444(7122):1038-43. PMID:17183314 doi:nature05456
  5. ↑ Svendsen JM, Smogorzewska A, Sowa ME, O'Connell BC, Gygi SP, Elledge SJ, Harper JW. Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell. 2009 Jul 10;138(1):63-77. PMID:19596235 doi:S0092-8674(09)00777-6

2a1j, resolution 2.70Å

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