8r79: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8r79 is ON HOLD
+==The D2 domain of human DTX3L==
+<StructureSection load='8r79' size='340' side='right'caption='[[8r79]], [[Resolution|resolution]] 2.18&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8r79]] 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=8R79 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8R79 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]] 2.18&#8491;</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=8r79 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8r79 OCA], [https://pdbe.org/8r79 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8r79 RCSB], [https://www.ebi.ac.uk/pdbsum/8r79 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8r79 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DTX3L_HUMAN DTX3L_HUMAN] Ubiquitin ligase that mediates monoubiquitination of 'Lys-91' of histone H4 (H4K91ub1), in response to DNA damage. Protects cells exposed to DNA-damaging agents. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 'Lys-20' methylation (H4K20me). Involved in the recruitment of 53BP1/TP53BP1 to sites of DNA damage by mediating H4K91ub1 formation. In concert with PARP9, plays a role in PARP1-dependent DNA damage repair. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites.<ref>PMID:12670957</ref> <ref>PMID:19818714</ref> <ref>PMID:23230272</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Deltex proteins are a family of E3 ubiquitin ligases that encode C-terminal RING and DTC domains that mediate interactions with E2 ubiquitin-conjugating enzymes and recognise ubiquitination substrates. DTX3L is unique among the Deltex proteins based on its N-terminal domain architecture. The N-terminal D1 and D2 domains of DTX3L mediate homo-oligomerisation, and the D3 domain interacts with PARP9, a protein that contains tandem macrodomains with ADP-ribose reader function. While DTX3L and PARP9 are known to heterodimerize, they assemble into a high molecular weight oligomeric complex, but the nature of the oligomeric structure, including whether this contributes to the ADP-ribose reader function is unknown. Here, we report a crystal structure of the DTX3L N-terminal D2 domain and show that it forms a tetramer with, conveniently, D2 symmetry. We identified two interfaces in the structure: a major, conserved interface with a surface of 973 A(2) and a smaller one of 415 A(2). Using native mass spectrometry, we observed molecular species that correspond to monomers, dimers and tetramers of the D2 domain. Reconstitution of DTX3L knockout cells with a D1-D2 deletion mutant showed the domain is dispensable for DTX3L-PARP9 heterodimer formation, but necessary to assemble an oligomeric complex with efficient reader function for ADP-ribosylated androgen receptor. Our results suggest that homo-oligomerisation of DTX3L is important for mono-ADP-ribosylation reading by the DTX3L-PARP9 complex and to a ligand-regulated transcription factor.
-Authors:
+Oligomerisation mediated by the D2 domain of DTX3L is critical for DTX3L-PARP9 reading function of mono-ADP-ribosylated androgen receptor.,Vela-Rodriguez C, Yang C, Alanen HI, Eki R, Abbas TA, Maksimainen MM, Glumoff T, Duman R, Wagner A, Paschal BM, Lehtio L bioRxiv. 2023 Nov 29:2023.11.29.569193. doi: 10.1101/2023.11.29.569193. Preprint. PMID:38076829<ref>PMID:38076829</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8r79" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Duman R]]
+[[Category: Glumoff T]]
+[[Category: Lehtio L]]
+[[Category: Maksimainen M]]
+[[Category: Vela-Rodriguez C]]
+[[Category: Wagner A]]