4d2h
From Proteopedia
(Difference between revisions)
| (4 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Crystal structure of the tetramerisation domain of human CtIP== |
| + | <StructureSection load='4d2h' size='340' side='right'caption='[[4d2h]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4d2h]] is a 8 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=4D2H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D2H 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]] 1.9Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4d2h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d2h OCA], [https://pdbe.org/4d2h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d2h RCSB], [https://www.ebi.ac.uk/pdbsum/4d2h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d2h ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/CTIP_HUMAN CTIP_HUMAN] Seckel syndrome;Jawad syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Genetic variability in RBBP8 is noted as a factor in BRCA1-associated breast cancer risk (PubMed:21799032). Associated with sensitivity to tamoxifen in certain breast cancer cell lines (PubMed:18171986).<ref>PMID:18171986</ref> <ref>PMID:21799032</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CTIP_HUMAN CTIP_HUMAN] Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway. HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse. Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ). Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA. Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage (PubMed:10764811, PubMed:10910365, PubMed:15485915, PubMed:16581787, PubMed:16818604, PubMed:17965729, PubMed:19202191, PubMed:19759395, PubMed:20064462, PubMed:20829486). During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (By similarity).[UniProtKB:Q80YR6]<ref>PMID:10764811</ref> <ref>PMID:10910365</ref> <ref>PMID:15485915</ref> <ref>PMID:16581787</ref> <ref>PMID:16818604</ref> <ref>PMID:17965729</ref> <ref>PMID:19202191</ref> <ref>PMID:19759395</ref> <ref>PMID:20064462</ref> <ref>PMID:20829486</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Mammalian CtIP protein has major roles in DNA double-strand break (DSB) repair. Although it is well established that CtIP promotes DNA-end resection in preparation for homology-dependent DSB repair, the molecular basis for this function has remained unknown. Here we show by biophysical and X-ray crystallographic analyses that the N-terminal domain of human CtIP exists as a stable homotetramer. Tetramerization results from interlocking interactions between the N-terminal extensions of CtIP's coiled-coil region, which lead to a 'dimer-of-dimers' architecture. Through interrogation of the CtIP structure, we identify a point mutation that abolishes tetramerization of the N-terminal domain while preserving dimerization in vitro. Notably, we establish that this mutation abrogates CtIP oligomer assembly in cells, thus leading to strong defects in DNA-end resection and gene conversion. These findings indicate that the CtIP tetramer architecture described here is essential for effective DSB repair by homologous recombination. | ||
| - | + | CtIP tetramer assembly is required for DNA-end resection and repair.,Davies OR, Forment JV, Sun M, Belotserkovskaya R, Coates J, Galanty Y, Demir M, Morton CR, Rzechorzek NJ, Jackson SP, Pellegrini L Nat Struct Mol Biol. 2015 Jan 5. doi: 10.1038/nsmb.2937. PMID:25558984<ref>PMID:25558984</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 4d2h" style="background-color:#fffaf0;"></div> |
| - | [[Category: Davies | + | |
| - | [[Category: Pellegrini | + | ==See Also== |
| + | *[[Retinoblastoma-binding protein 3D structures|Retinoblastoma-binding protein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Davies OR]] | ||
| + | [[Category: Pellegrini L]] | ||
| + | [[Category: Sun M]] | ||
Current revision
Crystal structure of the tetramerisation domain of human CtIP
| |||||||||||
