9c5v
From Proteopedia
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- | '''Unreleased structure''' | ||
- | + | ==Cryo EM structure of a DCAF2:degrader:BRD4 ternary complex== | |
- | + | <StructureSection load='9c5v' size='340' side='right'caption='[[9c5v]], [[Resolution|resolution]] 3.36Å' scene=''> | |
- | + | == Structural highlights == | |
- | + | <table><tr><td colspan='2'>[[9c5v]] is a 4 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=9C5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9C5V FirstGlance]. <br> | |
- | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.36Å</td></tr> | |
- | [[Category: | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AUO:N-({4-[(4-{[1-(chloroacetyl)-3-oxo-3,4-dihydro-1H-spiro[cyclopentane-1,2-quinoxalin]-6-yl]oxy}piperidin-1-yl)methyl]phenyl}methyl)-2-[(6S,10P)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetamide'>A1AUO</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=9c5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9c5v OCA], [https://pdbe.org/9c5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9c5v RCSB], [https://www.ebi.ac.uk/pdbsum/9c5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9c5v ProSAT]</span></td></tr> | ||
+ | </table> | ||
+ | == Function == | ||
+ | [https://www.uniprot.org/uniprot/DTL_HUMAN DTL_HUMAN] Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBH1, KMT5A and SDE2 (PubMed:16861906, PubMed:16949367, PubMed:16964240, PubMed:17085480, PubMed:18703516, PubMed:18794347, PubMed:18794348, PubMed:19332548, PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613, PubMed:27906959). CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication (PubMed:16861906, PubMed:16949367, PubMed:17085480). CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing (PubMed:18794348, PubMed:19332548). KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration (PubMed:23478445). Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis (PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207).<ref>PMID:16861906</ref> <ref>PMID:16949367</ref> <ref>PMID:16964240</ref> <ref>PMID:17085480</ref> <ref>PMID:18703516</ref> <ref>PMID:18794347</ref> <ref>PMID:18794348</ref> <ref>PMID:19332548</ref> <ref>PMID:20129063</ref> <ref>PMID:23478441</ref> <ref>PMID:23478445</ref> <ref>PMID:23677613</ref> <ref>PMID:26431207</ref> <ref>PMID:27906959</ref> | ||
+ | == References == | ||
+ | <references/> | ||
+ | __TOC__ | ||
+ | </StructureSection> | ||
+ | [[Category: Homo sapiens]] | ||
+ | [[Category: Large Structures]] | ||
+ | [[Category: McMahon EJ]] | ||
+ | [[Category: Wang W]] |
Current revision
Cryo EM structure of a DCAF2:degrader:BRD4 ternary complex
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