View source for 7nsc


==Substrate receptor scaffolding module of human CTLH E3 ubiquitin ligase==
<StructureSection load='7nsc' size='340' side='right'caption='[[7nsc]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7nsc]] 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=7NSC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NSC 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]] 3.3&#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=7nsc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nsc OCA], [https://pdbe.org/7nsc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nsc RCSB], [https://www.ebi.ac.uk/pdbsum/7nsc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nsc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RANB9_HUMAN RANB9_HUMAN] May act as an adapter protein to couple membrane receptors to intracellular signaling pathways. May be involved in signaling of ITGB2/LFA-1 and other integrins. Enhances HGF-MET signaling by recruiting Sos and activating the Ras pathway. Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but not affect estrogen-induced transactivation. Stabilizes TP73 isoform Alpha, probably by inhibiting its ubiquitination, and increases its proapoptotic activity. Inhibits the kinase activity of DYRK1A and DYRK1B. Inhibits FMR1 binding to RNA (By similarity).<ref>PMID:12147692</ref> <ref>PMID:12361945</ref> <ref>PMID:14500717</ref> <ref>PMID:14722085</ref> <ref>PMID:15381419</ref> <ref>PMID:15558019</ref> <ref>PMID:18222118</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
How are E3 ubiquitin ligases configured to match substrate quaternary structures? Here, by studying the yeast GID complex (mutation of which causes deficiency in glucose-induced degradation of gluconeogenic enzymes), we discover supramolecular chelate assembly as an E3 ligase strategy for targeting an oligomeric substrate. Cryoelectron microscopy (cryo-EM) structures show that, to bind the tetrameric substrate fructose-1,6-bisphosphatase (Fbp1), two minimally functional GID E3s assemble into the 20-protein Chelator-GID(SR4), which resembles an organometallic supramolecular chelate. The Chelator-GID(SR4) assembly avidly binds multiple Fbp1 degrons so that multiple Fbp1 protomers are simultaneously ubiquitylated at lysines near the allosteric and substrate binding sites. Importantly, key structural and biochemical features, including capacity for supramolecular assembly, are preserved in the human ortholog, the CTLH E3. Based on our integrative structural, biochemical, and cell biological data, we propose that higher-order E3 ligase assembly generally enables multipronged targeting, capable of simultaneously incapacitating multiple protomers and functionalities of oligomeric substrates.

GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme.,Sherpa D, Chrustowicz J, Qiao S, Langlois CR, Hehl LA, Gottemukkala KV, Hansen FM, Karayel O, von Gronau S, Prabu JR, Mann M, Alpi AF, Schulman BA Mol Cell. 2021 Apr 22. pii: S1097-2765(21)00220-3. doi:, 10.1016/j.molcel.2021.03.025. PMID:33905682<ref>PMID:33905682</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7nsc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chrustowicz J]]
[[Category: Prabu JR]]
[[Category: Schulman BA]]
[[Category: Sherpa D]]