2a1j: Difference between revisions

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-[[Image:2a1j.gif|left|200px]]<br />
-<applet load="2a1j" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2a1j, resolution 2.70&Aring;" />
-'''Crystal Structure of the Complex between the C-Terminal Domains of Human XPF and ERCC1'''<br />
-==Overview==
+==Crystal Structure of the Complex between the C-Terminal Domains of Human XPF and ERCC1==
-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.
+<StructureSection load='2a1j' size='340' side='right'caption='[[2a1j]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+== Structural highlights ==
+<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>
+</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>
+<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>
-==Disease==
+==See Also==
-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]]
+*[[Endonuclease 3D structures|Endonuclease 3D structures]]
+== References ==
-==About this Structure==
+<references/>
-A1J is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with HG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2A1J OCA].
+__TOC__
+</StructureSection>
-==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://ispc.weizmann.ac.il//pmbin/getpm?pmid=16076955 16076955]
 [[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://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:44:35 2007''