View source for 9ylf


==Cryo-EM structure of single-loaded human UBA6-UBE2Z/Ub(a) adenylate complex.==
<StructureSection load='9ylf' size='340' side='right'caption='[[9ylf]], [[Resolution|resolution]] 3.14&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ylf]] 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=9YLF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9YLF 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]] 3.14&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <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=9ylf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ylf OCA], [https://pdbe.org/9ylf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ylf RCSB], [https://www.ebi.ac.uk/pdbsum/9ylf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ylf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UBA6_HUMAN UBA6_HUMAN] Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Specific for ubiquitin, does not activate ubiquitin-like peptides. Differs from UBE1 in its specificity for substrate E2 charging. Does not charge cell cycle E2s, such as CDC34. Essential for embryonic development. Required for UBD/FAT10 conjugation. Isoform 2 may play a key role in ubiquitin system and may influence spermatogenesis and male fertility.<ref>PMID:15202508</ref> <ref>PMID:17597759</ref> <ref>PMID:17889673</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
UBA1 and UBA6 define parallel ubiquitin (Ub) activation systems that perform non-overlapping roles in Ub and ubiquitin-like protein (Ubl) signaling. Whereas UBA1 supports the canonical Ub pathway, UBA6 also activates the Ubl FAT10, linking Ub signaling to immune-regulated proteostasis. In addition to selective Ub/Ubl activation, UBA1 and UBA6 engage distinct sets of E2s, yet how these enzymes achieve selective E2 engagement has remained unclear. Using chemical trapping and high-resolution cryo-EM, we determine four structures of UBA6-E2 complexes representing the thioester-transfer step with either FAT10 or Ub, revealing how this E1 distinguishes its cognate partners. UBA6 achieves E2 specificity through coordinated contributions of the UFD and SCCH domains, a dual-domain mechanism that contrasts with the UFD-dominated selectivity of UBA1. The structures further show that an existing inositol hexakisphosphate (InsP(6))-binding site, unique to UBA6, stabilizes an expanded SCCH cleft that pre-organizes the enzyme for selective engagement of UBA6-specific E2s. These findings define principles for E1-E2 recognition and identify InsP(6) as a cofactor shaping specificity within the Ub-like conjugation network.

Cryo-EM structures of UBA6 reveal mechanisms of E1-E2 specificity and dual FAT10/ubiquitin thioester transfer.,Nayak D, Jia L, Dos Santos Bury P, Ruben EA, Shukla A, Nayak A, Stratton CM, Ebadi P, Cho H, Tumanova AA, Varughese JT, Yuan L, Gao F, Cano KE, Davies C, Sung P, Gack MU, Wasmuth EV, Olsen SK Nat Commun. 2026 Feb 28;17(1):3302. doi: 10.1038/s41467-026-69882-3. PMID:41764162<ref>PMID:41764162</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9ylf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bury PS]]
[[Category: Jia L]]
[[Category: Nayak D]]
[[Category: Olsen SK]]
[[Category: Ruben EA]]
[[Category: Wasmuth EV]]