View source for 4xi6


==Crystal structure of the MZM-REP domains of Mind bomb 1==
<StructureSection load='4xi6' size='340' side='right'caption='[[4xi6]], [[Resolution|resolution]] 2.04&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4xi6]] is a 1 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=4XI6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XI6 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.04&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <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=4xi6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xi6 OCA], [https://pdbe.org/4xi6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xi6 RCSB], [https://www.ebi.ac.uk/pdbsum/4xi6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xi6 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MIB1_HUMAN MIB1_HUMAN] Left ventricular noncompaction. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/MIB1_HUMAN MIB1_HUMAN] E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors. Probably mediates ubiquitination and subsequent proteasomal degradation of DAPK1, thereby antagonizing anti-apoptotic effects of DAPK1 to promote TNF-induced apoptosis (By similarity). Involved in ubiquitination of centriolar satellite CEP131, CEP290 and PCM1 proteins and hence inhibits primary cilium formation in proliferating cells. Mediates 'Lys-63'-linked polyubiquitination of TBK1, which probably participates in kinase activation.<ref>PMID:24121310</ref> 
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== Publication Abstract from PubMed ==
Mind bomb (Mib) proteins are large, multi-domain E3 ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. This ubiquitination step marks the ligand proteins for epsin-dependent endocytosis, which is critical for in vivo Notch receptor activation. We present here crystal structures of the substrate recognition domains of Mib1, both in isolation and in complex with peptides derived from Notch ligands. The structures, in combination with biochemical, cellular, and in vivo assays, show that Mib1 contains two independent substrate recognition domains that engage two distinct epitopes from the cytoplasmic tail of the ligand Jagged1, one in the intracellular membrane proximal region and the other near the C terminus. Together, these studies provide insights into the mechanism of ubiquitin transfer by Mind bomb E3 ligases, illuminate a key event in ligand-induced activation of Notch receptors, and identify a potential target for therapeutic modulation of Notch signal transduction in disease.

A tail of two sites: a bipartite mechanism for recognition of notch ligands by mind bomb e3 ligases.,McMillan BJ, Schnute B, Ohlenhard N, Zimmerman B, Miles L, Beglova N, Klein T, Blacklow SC Mol Cell. 2015 Mar 5;57(5):912-24. doi: 10.1016/j.molcel.2015.01.019. PMID:25747658<ref>PMID:25747658</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4xi6" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Blacklow SC]]
[[Category: McMillan BJ]]