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New page: left|200px<br /><applet load="1s8e" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s8e, resolution 2.3Å" /> '''Crystal structure of ...
 
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[[Image:1s8e.jpg|left|200px]]<br /><applet load="1s8e" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1s8e, resolution 2.3&Aring;" />
'''Crystal structure of Mre11-3'''<br />


==Overview==
==Crystal structure of Mre11-3==
The Mre11, Rad50 and Nbs1 proteins make up the conserved multi-functional, Mre11 (MRN) complex involved in multiple, critical DNA metabolic processes, including double-strand break repair and telomere maintenance. The Mre11, protein is a nuclease with broad substrate recognition, but MRN-dependent, processes requiring the nuclease activity are not clearly defined. Here, we report the functional and structural characterization of a, nuclease-deficient Mre11 protein termed mre11-3. Importantly, the hmre11-3, protein has wild-type ability to bind DNA, Rad50 and Nbs1; however, nuclease activity was completely abrogated. When expressed in cell lines, from patients with ataxia telangiectasia-like disorder (ATLD), hmre11-3, restored the formation of ionizing radiation-induced foci. Consistent with, the biochemical results, the 2.3 A crystal structure of mre11-3 from, Pyrococcus furiosus revealed an active site structure with a, wild-type-like metal-binding environment. The structural analysis of the, H85L mutation provides a detailed molecular basis for the ability of, mre11-3 to bind but not hydrolyze DNA. Together, these results establish, that the mre11-3 protein provides an excellent system for dissecting, nuclease-dependent and independent functions of the Mre11 complex.
<StructureSection load='1s8e' size='340' side='right'caption='[[1s8e]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1s8e]] is a 2 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=1S8E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S8E 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=1s8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s8e OCA], [https://pdbe.org/1s8e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s8e RCSB], [https://www.ebi.ac.uk/pdbsum/1s8e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s8e ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MRE11_PYRFU MRE11_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.
== 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/s8/1s8e_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=1s8e ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Mre11, Rad50 and Nbs1 proteins make up the conserved multi-functional Mre11 (MRN) complex involved in multiple, critical DNA metabolic processes including double-strand break repair and telomere maintenance. The Mre11 protein is a nuclease with broad substrate recognition, but MRN-dependent processes requiring the nuclease activity are not clearly defined. Here, we report the functional and structural characterization of a nuclease-deficient Mre11 protein termed mre11-3. Importantly, the hmre11-3 protein has wild-type ability to bind DNA, Rad50 and Nbs1; however, nuclease activity was completely abrogated. When expressed in cell lines from patients with ataxia telangiectasia-like disorder (ATLD), hmre11-3 restored the formation of ionizing radiation-induced foci. Consistent with the biochemical results, the 2.3 A crystal structure of mre11-3 from Pyrococcus furiosus revealed an active site structure with a wild-type-like metal-binding environment. The structural analysis of the H85L mutation provides a detailed molecular basis for the ability of mre11-3 to bind but not hydrolyze DNA. Together, these results establish that the mre11-3 protein provides an excellent system for dissecting nuclease-dependent and independent functions of the Mre11 complex.


==About this Structure==
Structural and functional analysis of Mre11-3.,Arthur LM, Gustausson K, Hopfner KP, Carson CT, Stracker TH, Karcher A, Felton D, Weitzman MD, Tainer J, Carney JP Nucleic Acids Res. 2004 Mar 26;32(6):1886-93. Print 2004. PMID:15047855<ref>PMID:15047855</ref>
1S8E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pyrococcus_furiosus Pyrococcus furiosus] with MN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S8E OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Structural and functional analysis of Mre11-3., Arthur LM, Gustausson K, Hopfner KP, Carson CT, Stracker TH, Karcher A, Felton D, Weitzman MD, Tainer J, Carney JP, Nucleic Acids Res. 2004 Mar 26;32(6):1886-93. Print 2004. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15047855 15047855]
</div>
[[Category: Pyrococcus furiosus]]
<div class="pdbe-citations 1s8e" style="background-color:#fffaf0;"></div>
[[Category: Single protein]]
== References ==
[[Category: Hopfner, K.P.]]
<references/>
[[Category: MN]]
__TOC__
[[Category: dna double-strand break]]
</StructureSection>
[[Category: mre11]]
[[Category: Large Structures]]
[[Category: rad50]]
[[Category: Pyrococcus furiosus DSM 3638]]
 
[[Category: Hopfner KP]]
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Retrieved from "https://proteopedia.org/1s8e"