7lw9: Difference between revisions
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==== | ==Human Exonuclease 5 crystal structure in complex with ssDNA, Sm, and Na== | ||
<StructureSection load='7lw9' size='340' side='right'caption='[[7lw9]]' scene=''> | <StructureSection load='7lw9' size='340' side='right'caption='[[7lw9]], [[Resolution|resolution]] 2.71Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7lw9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LW9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LW9 FirstGlance]. <br> | ||
</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=7lw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lw9 OCA], [https://pdbe.org/7lw9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lw9 RCSB], [https://www.ebi.ac.uk/pdbsum/7lw9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lw9 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.71Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=SM:SAMARIUM+(III)+ION'>SM</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=7lw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lw9 OCA], [https://pdbe.org/7lw9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lw9 RCSB], [https://www.ebi.ac.uk/pdbsum/7lw9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lw9 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/EXO5_HUMAN EXO5_HUMAN] Single-stranded DNA (ssDNA) bidirectional exonuclease involved in DNA repair. Probably involved in DNA repair following ultraviolet (UV) irradiation and interstrand cross-links (ICLs) damage. Has both 5'-3' and 3'-5' exonuclease activities with a strong preference for 5'-ends. Acts as a sliding exonuclease that loads at ssDNA ends and then slides along the ssDNA prior to cutting; however the sliding and the 3'-5' exonuclease activities are abolished upon binding to the replication protein A (RPA) complex that enforces 5'-directionality activity.<ref>PMID:23095756</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Stalled DNA replication fork restart after stress as orchestrated by ATR kinase, BLM helicase, and structure-specific nucleases enables replication, cell survival, and genome stability. Here we unveil human exonuclease V (EXO5) as an ATR-regulated DNA structure-specific nuclease and BLM partner for replication fork restart. We find that elevated EXO5 in tumors correlates with increased mutation loads and poor patient survival, suggesting that EXO5 upregulation has oncogenic potential. Structural, mechanistic, and mutational analyses of EXO5 and EXO5-DNA complexes reveal a single-stranded DNA binding channel with an adjacent ATR phosphorylation motif (T88Q89) that regulates EXO5 nuclease activity and BLM binding identified by mass spectrometric analysis. EXO5 phospho-mimetic mutant rescues the restart defect from EXO5 depletion that decreases fork progression, DNA damage repair, and cell survival. EXO5 depletion furthermore rescues survival of FANCA-deficient cells and indicates EXO5 functions epistatically with SMARCAL1 and BLM. Thus, an EXO5 axis connects ATR and BLM in directing replication fork restart. | |||
EXO5-DNA structure and BLM interactions direct DNA resection critical for ATR-dependent replication restart.,Hambarde S, Tsai CL, Pandita RK, Bacolla A, Maitra A, Charaka V, Hunt CR, Kumar R, Limbo O, Le Meur R, Chazin WJ, Tsutakawa SE, Russell P, Schlacher K, Pandita TK, Tainer JA Mol Cell. 2021 Jun 24. pii: S1097-2765(21)00420-2. doi:, 10.1016/j.molcel.2021.05.027. PMID:34197737<ref>PMID:34197737</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7lw9" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Exonuclease 3D structures|Exonuclease 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Synthetic construct]] | ||
[[Category: Tainer JA]] | |||
[[Category: Tsai CL]] | |||