7lin: Difference between revisions
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==== | ==X-ray structure of SPOP MATH domain (D140G) in complex with a 53BP1 peptide== | ||
<StructureSection load='7lin' size='340' side='right'caption='[[7lin]]' scene=''> | <StructureSection load='7lin' size='340' side='right'caption='[[7lin]], [[Resolution|resolution]] 1.44Å' 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'>[[7lin]] 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=7LIN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LIN 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=7lin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lin OCA], [https://pdbe.org/7lin PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lin RCSB], [https://www.ebi.ac.uk/pdbsum/7lin PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lin 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]] 1.44Å</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=7lin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lin OCA], [https://pdbe.org/7lin PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lin RCSB], [https://www.ebi.ac.uk/pdbsum/7lin PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lin ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/SPOP_HUMAN SPOP_HUMAN] Inhibits IPF1/PDX1 transactivation of established target promoters, such as insulin, may be by recruiting a repressor complex (By similarity). In complex with CUL3, involved in ubiquitination of BMI1, H2AFY and DAXX, and probably also in ubiquitination and proteasomal degradation of Gli2 or Gli3.<ref>PMID:14528312</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
53BP1 activates nonhomologous end joining (NHEJ) and inhibits homologous recombination (HR) repair of DNA double-strand breaks (DSBs). Dissociation of 53BP1 from DSBs and consequent activation of HR, a less error-prone pathway than NHEJ, helps maintain genome integrity during DNA replication; however, the underlying mechanisms are not fully understood. Here, we demonstrate that E3 ubiquitin ligase SPOP promotes HR during S phase of the cell cycle by excluding 53BP1 from DSBs. In response to DNA damage, ATM kinase-catalyzed phosphorylation of SPOP causes a conformational change in SPOP, revealed by x-ray crystal structures, that stabilizes its interaction with 53BP1. 53BP1-bound SPOP induces polyubiquitination of 53BP1, eliciting 53BP1 extraction from chromatin by a valosin-containing protein/p97 segregase complex. Our work shows that SPOP facilitates HR repair over NHEJ during DNA replication by contributing to 53BP1 removal from chromatin. Cancer-derived SPOP mutations block SPOP interaction with 53BP1, inducing HR defects and chromosomal instability. | |||
ATM-phosphorylated SPOP contributes to 53BP1 exclusion from chromatin during DNA replication.,Wang D, Ma J, Botuyan MV, Cui G, Yan Y, Ding D, Zhou Y, Krueger EW, Pei J, Wu X, Wang L, Pei H, McNiven MA, Ye D, Mer G, Huang H Sci Adv. 2021 Jun 18;7(25). pii: 7/25/eabd9208. doi: 10.1126/sciadv.abd9208., Print 2021 Jun. PMID:34144977<ref>PMID:34144977</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7lin" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Speckle-type POZ protein 3D structures|Speckle-type POZ protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Botuyan MV]] | ||
[[Category: Cui G]] | |||
[[Category: Mer G]] | |||