View source for 7z8b


==Structure of CRL7FBXW8 reveals coupling with CUL1-RBX1/ROC1 for multi-cullin-RING E3-catalyzed ubiquitin ligation==
<StructureSection load='7z8b' size='340' side='right'caption='[[7z8b]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7z8b]] is a 4 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=7Z8B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z8B 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]] 2.8&#8491;</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=7z8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z8b OCA], [https://pdbe.org/7z8b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z8b RCSB], [https://www.ebi.ac.uk/pdbsum/7z8b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z8b ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CUL7_HUMAN CUL7_HUMAN] Defects in CUL7 are the cause of 3M syndrome type 1 (3M1) [MIM:[https://omim.org/entry/273750 273750]. An autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, facial dysmorphism, large head circumference, and normal intelligence and endocrine function. Skeletal changes include long slender tubular bones and tall vertebral bodies.<ref>PMID:16142236</ref> 
== Function ==
[https://www.uniprot.org/uniprot/CUL7_HUMAN CUL7_HUMAN] Component of a probable SCF-like E3 ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably plays a role in the degradation of proteins involved in endothelial proliferation and/or differentiation (By similarity). Seems not to promote polyubiquitination and proteasomal degradation of TP53. In vitro, complexes of CUL7 with either CUL9 or FBXW8 or TP53 contain E3 ubiquitin-protein ligase activity.<ref>PMID:16547496</ref> <ref>PMID:17332328</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Most cullin-RING ubiquitin ligases (CRLs) form homologous assemblies between a neddylated cullin-RING catalytic module and a variable substrate-binding receptor (for example, an F-box protein). However, the vertebrate-specific CRL7(FBXW8) is of interest because it eludes existing models, yet its constituent cullin CUL7 and F-box protein FBXW8 are essential for development, and CUL7 mutations cause 3M syndrome. In this study, cryo-EM and biochemical analyses reveal the CRL7(FBXW8) assembly. CUL7's exclusivity for FBXW8 among all F-box proteins is explained by its unique F-box-independent binding mode. In CRL7(FBXW8), the RBX1 (also known as ROC1) RING domain is constrained in an orientation incompatible with binding E2~NEDD8 or E2~ubiquitin intermediates. Accordingly, purified recombinant CRL7(FBXW8) lacks auto-neddylation and ubiquitination activities. Instead, our data indicate that CRL7 serves as a substrate receptor linked via SKP1-FBXW8 to a neddylated CUL1-RBX1 catalytic module mediating ubiquitination. The structure reveals a distinctive CRL-CRL partnership, and provides a framework for understanding CUL7 assemblies safeguarding human health.

Structure of CRL7(FBXW8) reveals coupling with CUL1-RBX1/ROC1 for multi-cullin-RING E3-catalyzed ubiquitin ligation.,Hopf LVM, Baek K, Klugel M, von Gronau S, Xiong Y, Schulman BA Nat Struct Mol Biol. 2022 Sep;29(9):854-862. doi: 10.1038/s41594-022-00815-6. , Epub 2022 Aug 18. PMID:35982156<ref>PMID:35982156</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7z8b" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cullin 3D structures|Cullin 3D structures]]
*[[Ring box protein 3D structures|Ring box protein 3D structures]]
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hopf LVM]]
[[Category: Schulman BA]]