8cdk: Difference between revisions
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==CAND1 b-hairpin++-SCF-SKP2 CAND1 partly engaged SCF partly rocked== | |||
<StructureSection load='8cdk' size='340' side='right'caption='[[8cdk]], [[Resolution|resolution]] 3.32Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8cdk]] 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=8CDK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CDK 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> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8cdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cdk OCA], [https://pdbe.org/8cdk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cdk RCSB], [https://www.ebi.ac.uk/pdbsum/8cdk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cdk ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SKP2_HUMAN SKP2_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 involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, MLL, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-Dependent Manner, thereby regulating cell migration.<ref>PMID:12435635</ref> <ref>PMID:11931757</ref> <ref>PMID:12840033</ref> <ref>PMID:12769844</ref> <ref>PMID:15342634</ref> <ref>PMID:16262255</ref> <ref>PMID:15949444</ref> <ref>PMID:16103164</ref> <ref>PMID:15668399</ref> <ref>PMID:16951159</ref> <ref>PMID:16581786</ref> <ref>PMID:17908926</ref> <ref>PMID:17962192</ref> <ref>PMID:22770219</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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 Mar 31:S0092-8674(23)00213-1. doi: 10.1016/j.cell.2023.02.035. PMID:37028429<ref>PMID:37028429</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8cdk" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Baek K]] | |||
[[Category: Schulman BA]] |