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| | ==Crystal Structure of Pyrococcus furiosis Rad50 R805E mutation== | | ==Crystal Structure of Pyrococcus furiosis Rad50 R805E mutation== |
| - | <StructureSection load='4nci' size='340' side='right' caption='[[4nci]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='4nci' size='340' side='right'caption='[[4nci]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4nci]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pyrfu Pyrfu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NCI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4nci]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_furiosus_DSM_3638 Pyrococcus furiosus DSM 3638]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NCI FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nch|4nch]], [[4ncj|4ncj]], [[4nck|4nck]]</td></tr> | + | </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=4nci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nci OCA], [https://pdbe.org/4nci PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nci RCSB], [https://www.ebi.ac.uk/pdbsum/4nci PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nci ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PF1167, rad50 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=186497 PYRFU])</td></tr>
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| - | <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=4nci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nci OCA], [http://pdbe.org/4nci PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nci RCSB], [http://www.ebi.ac.uk/pdbsum/4nci PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nci ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RAD50_PYRFU RAD50_PYRFU]] Involved in DNA double-strand break repair (DSBR). The Rad50/Mre11 complex possesses single-strand endonuclease activity and ATP-dependent double-strand-specific 3'-5' exonuclease activity. Rad50 provides an ATP-dependent control of Mre11 by unwinding and/or repositioning DNA ends into the Mre11 active site.[HAMAP-Rule:MF_00449] | + | [https://www.uniprot.org/uniprot/RAD50_PYRFU RAD50_PYRFU] Involved in DNA double-strand break repair (DSBR). The Rad50/Mre11 complex possesses single-strand endonuclease activity and ATP-dependent double-strand-specific 3'-5' exonuclease activity. Rad50 provides an ATP-dependent control of Mre11 by unwinding and/or repositioning DNA ends into the Mre11 active site.[HAMAP-Rule:MF_00449] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4nci" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4nci" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[ATPase 3D structures|ATPase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Pyrfu]] | + | [[Category: Large Structures]] |
| - | [[Category: Arvai, A S]] | + | [[Category: Pyrococcus furiosus DSM 3638]] |
| - | [[Category: Classen, S]] | + | [[Category: Arvai AS]] |
| - | [[Category: Williams, G J]] | + | [[Category: Classen S]] |
| - | [[Category: Williams, R S]] | + | [[Category: Williams GJ]] |
| - | [[Category: Adenosine triphosphatase]] | + | [[Category: Williams RS]] |
| - | [[Category: Dna binding protein]]
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| - | [[Category: Dna repair]]
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| - | [[Category: Fungal protein]]
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| Structural highlights
Function
RAD50_PYRFU Involved in DNA double-strand break repair (DSBR). The Rad50/Mre11 complex possesses single-strand endonuclease activity and ATP-dependent double-strand-specific 3'-5' exonuclease activity. Rad50 provides an ATP-dependent control of Mre11 by unwinding and/or repositioning DNA ends into the Mre11 active site.[HAMAP-Rule:MF_00449]
Publication Abstract from PubMed
The Mre11-Rad50 complex is highly conserved, yet the mechanisms by which Rad50 ATP-driven states regulate the sensing, processing and signaling of DNA double-strand breaks are largely unknown. Here we design structure-based mutations in Pyrococcus furiosus Rad50 to alter protein core plasticity and residues undergoing ATP-driven movements within the catalytic domains. With this strategy we identify Rad50 separation-of-function mutants that either promote or destabilize the ATP-bound state. Crystal structures, X-ray scattering, biochemical assays, and functional analyses of mutant PfRad50 complexes show that the ATP-induced 'closed' conformation promotes DNA end binding and end tethering, while hydrolysis-induced opening is essential for DNA resection. Reducing the stability of the ATP-bound state impairs DNA repair and Tel1 (ATM) checkpoint signaling in Schizosaccharomyces pombe, double-strand break resection in Saccharomyces cerevisiae, and ATM activation by human Mre11-Rad50-Nbs1 in vitro, supporting the generality of the P. furiosus Rad50 structure-based mutational analyses. These collective results suggest that ATP-dependent Rad50 conformations switch the Mre11-Rad50 complex between DNA tethering, ATM signaling, and 5' strand resection, revealing molecular mechanisms regulating responses to DNA double-strand breaks.
ATP-driven Rad50 conformations regulate DNA tethering, end resection, and ATM checkpoint signaling.,Deshpande RA, Williams GJ, Limbo O, Williams RS, Kuhnlein J, Lee JH, Classen S, Guenther G, Russell P, Tainer JA, Paull TT EMBO J. 2014 Mar 3;33(5):482-500. doi: 10.1002/embj.201386100. Epub 2014 Feb 3. PMID:24493214[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Deshpande RA, Williams GJ, Limbo O, Williams RS, Kuhnlein J, Lee JH, Classen S, Guenther G, Russell P, Tainer JA, Paull TT. ATP-driven Rad50 conformations regulate DNA tethering, end resection, and ATM checkpoint signaling. EMBO J. 2014 Mar 3;33(5):482-500. doi: 10.1002/embj.201386100. Epub 2014 Feb 3. PMID:24493214 doi:http://dx.doi.org/10.1002/embj.201386100
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