View source for 28mq


==Cryo-EM structure of UBA6-FAT10Dha-UBE2Z trapped ternary complex==
<StructureSection load='28mq' size='340' side='right'caption='[[28mq]], [[Resolution|resolution]] 3.04&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[28mq]] is a 3 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=28MQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=28MQ 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]] 3.04&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</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=28mq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=28mq OCA], [https://pdbe.org/28mq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=28mq RCSB], [https://www.ebi.ac.uk/pdbsum/28mq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=28mq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UBE2Z_HUMAN UBE2Z_HUMAN] Catalyzes the covalent attachment of ubiquitin to other proteins (By similarity). Specific substrate for UBA6, not charged with ubiquitin by UBE1. May be involved in apoptosis regulation.[PROSITE-ProRule:PRU00388]<ref>PMID:17464193</ref> <ref>PMID:17597759</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Attachment of the ubiquitin-like protein (UBL) FAT10 onto substrates targets them for proteasomal degradation. Like ubiquitin, FAT10 is activated by the E1 enzyme UBA6 then transferred to E2 enzymes, but mechanisms controlling ubiquitin versus FAT10 activation by UBA6 and FAT10 transfer onto E2s remain unclear. Using cryo-EM, we visualise all stages of FAT10 E1-E2 handover: adenylation, thiolation and transthiolation. We find that FAT10 monopolises UBA6 by out-competing ubiquitin for thiolation and blocking the adenylation domain, preventing further UBL recruitment and promoting FAT10 signalling. We profiled UBA6-compatible E2 enzymes and found FAT10 transfer is restricted to a select subset associated with specific cellular pathways. UBE2Z (USE1) showed highest activity followed by UBE2D2, UBE2J2 and UBE2S. Capturing FAT10 or ubiquitin transfer from UBA6 to UBE2Z reveals UBE2Z is highly specialised for FAT10 transfer. It simultaneously engages both FAT10 domains (UBL1 and UBL2) and co-ordinates the metabolite inositol hexakisphosphate (InsP(6)) bound within the UBA6 catalytic domain. This InsP(6) co-ordination extends to other FAT10 compatible E2s. Together, our structural and biochemical analyses reveal regulatory mechanisms underpinning FAT10 activation and transfer. We define principles governing selective FAT10 transfer, highlighting favourable interactions with FAT10 C-terminal domain (UBL2) and stable UBA6 binding, ensuring controlled conjugation onto substrates.

Structural determinants for FAT10 activation and transfer from UBA6 to E2 enzymes.,Ellison CJ, Riechmann C, Dalietou EV, Simmons MDR, Dodd EC, Elliott PR Nat Commun. 2026 Aug 13;17(1):9751. doi: 10.1038/s41467-026-76603-3. PMID:42733088<ref>PMID:42733088</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 28mq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Elliott PR]]
[[Category: Ellison CJ]]
[[Category: Riechmann C]]