6t7f
From Proteopedia
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| - | ==== | + | ==RCR E3 ligase E2-Ubiquitin transthiolation intermediate== |
| - | <StructureSection load='6t7f' size='340' side='right'caption='[[6t7f]]' scene=''> | + | <StructureSection load='6t7f' size='340' side='right'caption='[[6t7f]], [[Resolution|resolution]] 2.58Å' 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'>[[6t7f]] 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=6T7F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T7F 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]] 2.58Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LWZ:3,3-bis(sulfanyl)-~{N}-(1~{H}-1,2,3-triazol-4-ylmethyl)propanamide'>LWZ</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=6t7f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t7f OCA], [https://pdbe.org/6t7f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t7f RCSB], [https://www.ebi.ac.uk/pdbsum/6t7f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t7f ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MYCB2_HUMAN MYCB2_HUMAN] E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of TSC2/tuberin. Interacts with the E2 enzymes UBE2D1, UBE2D3 and UBE2L3 (in vitro). May function as a facilitator or regulator of transcriptional activation by MYC. May have a role during synaptogenesis.<ref>PMID:18308511</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | MYCBP2 is a ubiquitin (Ub) E3 ligase (E3) that is essential for neurodevelopment and regulates axon maintenance. MYCBP2 transfers Ub to nonlysine substrates via a newly discovered RING-Cys-Relay (RCR) mechanism, where Ub is relayed from an upstream cysteine to a downstream substrate esterification site. The molecular bases for E2-E3 Ub transfer and Ub relay are unknown. Whether these activities are linked to the neural phenotypes is also unclear. We describe the crystal structure of a covalently trapped E2~Ub:MYCBP2 transfer intermediate revealing key structural rearrangements upon E2-E3 Ub transfer and Ub relay. Our data suggest that transfer to the dynamic upstream cysteine, whilst mitigating lysine activity, requires a closed-like E2~Ub conjugate with tempered reactivity, and Ub relay is facilitated by a helix-coil transition. Furthermore, neurodevelopmental defects and delayed injury-induced degeneration in RCR-defective knock-in mice suggest its requirement, and that of substrate esterification activity, for normal neural development and programmed axon degeneration. | ||
| + | |||
| + | Structural basis for RING-Cys-Relay E3 ligase activity and its role in axon integrity.,Mabbitt PD, Loreto A, Dery MA, Fletcher AJ, Stanley M, Pao KC, Wood NT, Coleman MP, Virdee S Nat Chem Biol. 2020 Nov;16(11):1227-1236. doi: 10.1038/s41589-020-0598-6. Epub, 2020 Aug 3. PMID:32747811<ref>PMID:32747811</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6t7f" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] | ||
| + | *[[3D structures of ubiquitin|3D structures of ubiquitin]] | ||
| + | *[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Mabbitt PD]] |
| + | [[Category: Virdee S]] | ||
Revision as of 12:56, 24 January 2024
RCR E3 ligase E2-Ubiquitin transthiolation intermediate
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