7z8v
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7z8v]] is a 5 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=7Z8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z8V FirstGlance]. <br> | <table><tr><td colspan='2'>[[7z8v]] is a 5 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=7Z8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z8V FirstGlance]. <br> | ||
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.7Å</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=7z8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z8v OCA], [https://pdbe.org/7z8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z8v RCSB], [https://www.ebi.ac.uk/pdbsum/7z8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z8v ProSAT]</span></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=7z8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z8v OCA], [https://pdbe.org/7z8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z8v RCSB], [https://www.ebi.ac.uk/pdbsum/7z8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z8v ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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Cells respond to environmental cues by remodeling their inventories of multiprotein complexes. Cellular repertoires of SCF (SKP1-CUL1-F box protein) ubiquitin ligase complexes, which mediate much protein degradation, require CAND1 to distribute the limiting CUL1 subunit across the family of approximately 70 different F box proteins. Yet, how a single factor coordinately assembles numerous distinct multiprotein complexes remains unknown. We obtained cryo-EM structures of CAND1-bound SCF complexes in multiple states and correlated mutational effects on structures, biochemistry, and cellular assays. The data suggest that CAND1 clasps idling catalytic domains of an inactive SCF, rolls around, and allosterically rocks and destabilizes the SCF. New SCF production proceeds in reverse, through SKP1-F box allosterically destabilizing CAND1. The CAND1-SCF conformational ensemble recycles CUL1 from inactive complexes, fueling mixing and matching of SCF parts for E3 activation in response to substrate availability. Our data reveal biogenesis of a predominant family of E3 ligases, and the molecular basis for systemwide multiprotein complex assembly. | Cells respond to environmental cues by remodeling their inventories of multiprotein complexes. Cellular repertoires of SCF (SKP1-CUL1-F box protein) ubiquitin ligase complexes, which mediate much protein degradation, require CAND1 to distribute the limiting CUL1 subunit across the family of approximately 70 different F box proteins. Yet, how a single factor coordinately assembles numerous distinct multiprotein complexes remains unknown. We obtained cryo-EM structures of CAND1-bound SCF complexes in multiple states and correlated mutational effects on structures, biochemistry, and cellular assays. The data suggest that CAND1 clasps idling catalytic domains of an inactive SCF, rolls around, and allosterically rocks and destabilizes the SCF. New SCF production proceeds in reverse, through SKP1-F box allosterically destabilizing CAND1. The CAND1-SCF conformational ensemble recycles CUL1 from inactive complexes, fueling mixing and matching of SCF parts for E3 activation in response to substrate availability. Our data reveal biogenesis of a predominant family of E3 ligases, and the molecular basis for systemwide multiprotein complex assembly. | ||
| - | Systemwide disassembly and assembly of SCF ubiquitin ligase complexes.,Baek K, Scott DC, Henneberg LT, King MT, Mann M, Schulman BA Cell. 2023 | + | Systemwide disassembly and assembly of SCF ubiquitin ligase complexes.,Baek K, Scott DC, Henneberg LT, King MT, Mann M, Schulman BA Cell. 2023 Apr 27;186(9):1895-1911.e21. doi: 10.1016/j.cell.2023.02.035. Epub , 2023 Apr 6. PMID:37028429<ref>PMID:37028429</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 7z8v" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7z8v" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[CAND1 3D structures|CAND1 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
CAND1-SCF-SKP2 (SKP1deldel) CAND1 engaged SCF rocked
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