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==== | ==Crystal structure of Uba4-Urm1 from Chaetomium thermophilum== | ||
<StructureSection load='6yuc' size='340' side='right'caption='[[6yuc]]' scene=''> | <StructureSection load='6yuc' size='340' side='right'caption='[[6yuc]], [[Resolution|resolution]] 3.15Å' 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 [ | <table><tr><td colspan='2'>[[6yuc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chaetomium_thermophilum Chaetomium thermophilum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YUC FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.15Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6yuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yuc OCA], [https://pdbe.org/6yuc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yuc RCSB], [https://www.ebi.ac.uk/pdbsum/6yuc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yuc ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/G0SC54_CHATD G0SC54_CHATD] Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln). Also essential during biosynthesis of the molybdenum cofactor. Acts by mediating the C-terminal thiocarboxylation of sulfur carriers urm1 and MOCS2A. Its N-terminus first activates urm1 and MOCS2A as acyl-adenylates (-COAMP), then the persulfide sulfur on the catalytic cysteine is transferred to urm1 and MOCS2A to form thiocarboxylation (-COSH) of their C-terminus. The reaction probably involves hydrogen sulfide that is generated from the persulfide intermediate and that acts as nucleophile towards urm1 and MOCS2A. Subsequently, a transient disulfide bond is formed. Does not use thiosulfate as sulfur donor; nfs1 probably acting as a sulfur donor for thiocarboxylation reactions.[HAMAP-Rule:MF_03049] Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln). Also essential during biosynthesis of the molybdenum cofactor. Acts by mediating the C-terminal thiocarboxylation of sulfur carriers urm1 and mocs2a. Its N-terminus first activates urm1 and mocs2a as acyl-adenylates (-COAMP), then the persulfide sulfur on the catalytic cysteine is transferred to urm1 and mocs2a to form thiocarboxylation (-COSH) of their C-terminus. The reaction probably involves hydrogen sulfide that is generated from the persulfide intermediate and that acts as a nucleophile towards urm1 and mocs2a. Subsequently, a transient disulfide bond is formed. Does not use thiosulfate as sulfur donor; nfs1 probably acting as a sulfur donor for thiocarboxylation reactions.[ARBA:ARBA00043893] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The chemical modification of tRNA bases by sulfur is crucial to tune translation and to optimize protein synthesis. In eukaryotes, the ubiquitin-related modifier 1 (Urm1) pathway is responsible for the synthesis of 2-thiolated wobble uridine (U34 ). During the key step of the modification cascade, the E1-like activating enzyme ubiquitin-like protein activator 4 (Uba4) first adenylates and thiocarboxylates the C-terminus of its substrate Urm1. Subsequently, activated thiocarboxylated Urm1 (Urm1-COSH) can serve as a sulfur donor for specific tRNA thiolases or participate in ubiquitin-like conjugation reactions. Structural and mechanistic details of Uba4 and Urm1 have remained elusive but are key to understand the evolutionary branch point between ubiquitin-like proteins (UBL) and sulfur-relay systems. Here, we report the crystal structures of full-length Uba4 and its heterodimeric complex with its substrate Urm1. We show how the two domains of Uba4 orchestrate recognition, binding, and thiocarboxylation of the C-terminus of Urm1. Finally, we uncover how the catalytic domains of Uba4 communicate efficiently during the reaction cycle and identify a mechanism that enables Uba4 to protect itself against self-conjugation with its own product, namely activated Urm1-COSH. | |||
Molecular basis for the bifunctional Uba4-Urm1 sulfur-relay system in tRNA thiolation and ubiquitin-like conjugation.,Pabis M, Termathe M, Ravichandran KE, Kienast SD, Krutyholowa R, Sokolowski M, Jankowska U, Grudnik P, Leidel SA, Glatt S EMBO J. 2020 Sep 9:e105087. doi: 10.15252/embj.2020105087. PMID:32901956<ref>PMID:32901956</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6yuc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[3D structures of Ubiquitin activating enzyme|3D structures of Ubiquitin activating enzyme]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Chaetomium thermophilum]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Ethiraju Ravichandran K]] | ||
[[Category: Glatt S]] | |||
[[Category: Grudnik P]] | |||
[[Category: Pabis M]] | |||