View source for 8ua6


==Cryo-EM Structure of SCF-FBOX22-BACH1BTB==
<StructureSection load='8ua6' size='340' side='right'caption='[[8ua6]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ua6]] 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=8UA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UA6 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]] 3.9&#8491;</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=8ua6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ua6 OCA], [https://pdbe.org/8ua6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ua6 RCSB], [https://www.ebi.ac.uk/pdbsum/8ua6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ua6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FBX22_HUMAN FBX22_HUMAN] Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Promotes the proteasome-dependent degradation of key sarcomeric proteins, such as alpha-actinin (ACTN2) and filamin-C (FLNC), essential for maintenance of normal contractile function.<ref>PMID:22972877</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The transcription factor BACH1 regulates heme homeostasis and oxidative stress responses and promotes cancer metastasis upon aberrant accumulation. Its stability is controlled by two F-box protein ubiquitin ligases, FBXO22 and FBXL17. Here we show that the homodimeric BTB domain of BACH1 functions as a previously undescribed quaternary structure degron, which is deciphered by the two F-box proteins via distinct mechanisms. After BACH1 is released from chromatin by heme, FBXO22 asymmetrically recognizes a cross-protomer interface of the intact BACH1 BTB dimer, which is otherwise masked by the co-repressor NCOR1. If the BACH1 BTB dimer escapes the surveillance by FBXO22 due to oxidative modifications, its quaternary structure integrity is probed by a pair of FBXL17, which simultaneously engage and remodel the two BTB protomers into E3-bound monomers for ubiquitination. By unveiling the multifaceted regulatory mechanisms of BACH1 stability, our studies highlight the abilities of ubiquitin ligases to decode high-order protein assemblies and reveal therapeutic opportunities to block cancer invasion via compound-induced BACH1 destabilization.

Distinct Perception Mechanisms of BACH1 Quaternary Structure Degrons by Two F-box Proteins under Oxidative Stress.,Cao S, Shi H, Garcia SF, Kito Y, Shi H, Goldberg HV, Ponce J, Ueberheide B, Lignitto L, Pagano M, Zheng N bioRxiv [Preprint]. 2024 Jun 3:2024.06.03.594717. doi: 10.1101/2024.06.03.594717. PMID:38895309<ref>PMID:38895309</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ua6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cao S]]
[[Category: Shi H]]
[[Category: Zheng N]]