View source for 8pmq


==Catalytic module of yeast GID E3 ligase bound to multiphosphorylated Ubc8~ubiquitin==
<StructureSection load='8pmq' size='340' side='right'caption='[[8pmq]], [[Resolution|resolution]] 3.53&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8pmq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8PMQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PMQ 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]] 3.53&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <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=8pmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pmq OCA], [https://pdbe.org/8pmq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pmq RCSB], [https://www.ebi.ac.uk/pdbsum/8pmq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pmq ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ubiquitylation is catalyzed by coordinated actions of E3 and E2 enzymes. Molecular principles governing many important E3-E2 partnerships remain unknown, including those for RING-family GID/CTLH E3 ubiquitin ligases and their dedicated E2, Ubc8/UBE2H (yeast/human nomenclature). GID/CTLH-Ubc8/UBE2H-mediated ubiquitylation regulates biological processes ranging from yeast metabolic signaling to human development. Here, cryoelectron microscopy (cryo-EM), biochemistry, and cell biology reveal this exquisitely specific E3-E2 pairing through an unconventional catalytic assembly and auxiliary interactions 70-100 A away, mediated by E2 multisite phosphorylation. Rather than dynamic polyelectrostatic interactions reported for other ubiquitylation complexes, multiple Ubc8/UBE2H phosphorylation sites within acidic CK2-targeted sequences specifically anchor the E2 C termini to E3 basic patches. Positions of phospho-dependent interactions relative to the catalytic domains correlate across evolution. Overall, our data show that phosphorylation-dependent multivalency establishes a specific E3-E2 partnership, is antagonistic with dephosphorylation, rigidifies the catalytic centers within a flexing GID E3-substrate assembly, and facilitates substrate collision with ubiquitylation active sites.

Multisite phosphorylation dictates selective E2-E3 pairing as revealed by Ubc8/UBE2H-GID/CTLH assemblies.,Chrustowicz J, Sherpa D, Li J, Langlois CR, Papadopoulou EC, Vu DT, Hehl LA, Karayel O, Beier V, von Gronau S, Muller J, Prabu JR, Mann M, Kleiger G, Alpi AF, Schulman BA Mol Cell. 2024 Jan 18;84(2):293-308.e14. doi: 10.1016/j.molcel.2023.11.027. Epub , 2023 Dec 18. PMID:38113892<ref>PMID:38113892</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8pmq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Chrustowicz J]]
[[Category: Prabu RJ]]
[[Category: Schulman BA]]
[[Category: Sherpa D]]