7t1z
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| - | ==== | + | ==Structure of the Fbw7-Skp1-MycNdegron complex== |
| - | <StructureSection load='7t1z' size='340' side='right'caption='[[7t1z]]' scene=''> | + | <StructureSection load='7t1z' size='340' side='right'caption='[[7t1z]], [[Resolution|resolution]] 2.77Å' 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 [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7t1z]] 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=7T1Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T1Z FirstGlance]. <br> |
| - | </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=7t1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t1z OCA], [https://pdbe.org/7t1z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t1z RCSB], [https://www.ebi.ac.uk/pdbsum/7t1z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t1z ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.77Å</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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=7t1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t1z OCA], [https://pdbe.org/7t1z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t1z RCSB], [https://www.ebi.ac.uk/pdbsum/7t1z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t1z ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/FBXW7_HUMAN FBXW7_HUMAN] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably recognizes and binds to phosphorylated target proteins. Involved in the degradation of cyclin-E, MYC, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1.<ref>PMID:11565034</ref> <ref>PMID:11585921</ref> <ref>PMID:15103331</ref> <ref>PMID:17873522</ref> <ref>PMID:17558397</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | c-Myc (hereafter, Myc) is a cancer driver whose abundance is regulated by the SCF(Fbw7) ubiquitin ligase and proteasomal degradation. Fbw7 binds to a phosphorylated Myc degron centered at threonine 58 (T58), and mutations of Fbw7 or T58 impair Myc degradation in cancers. Here, we identify a second Fbw7 phosphodegron at Myc T244 that is required for Myc ubiquitylation and acts in concert with T58 to engage Fbw7. While Ras-dependent Myc serine 62 phosphorylation (pS62) is thought to stabilize Myc by preventing Fbw7 binding, we find instead that pS62 greatly enhances Fbw7 binding and is an integral part of a high-affinity degron. Crystallographic studies revealed that both degrons bind Fbw7 in their diphosphorylated forms and that the T244 degron is recognized via a unique mode involving Fbw7 arginine 689 (R689), a mutational hotspot in cancers. These insights have important implications for Myc-associated tumorigenesis and therapeutic strategies targeting Myc stability. | ||
| + | |||
| + | Two diphosphorylated degrons control c-Myc degradation by the Fbw7 tumor suppressor.,Welcker M, Wang B, Rusnac DV, Hussaini Y, Swanger J, Zheng N, Clurman BE Sci Adv. 2022 Jan 28;8(4):eabl7872. doi: 10.1126/sciadv.abl7872. Epub 2022 Jan , 28. PMID:35089787<ref>PMID:35089787</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7t1z" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Clurman BE]] |
| + | [[Category: Rusnac DV]] | ||
| + | [[Category: Wang B]] | ||
| + | [[Category: Zheng N]] | ||
Current revision
Structure of the Fbw7-Skp1-MycNdegron complex
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