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4xi7

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Revision as of 00:23, 26 January 2017

Crystal structure of the MZM-REP domains of Mind bomb 1 in complex with Jagged1 N-box peptide

Structural highlights

4xi7 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4xfx, 4xib
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MIB1_HUMAN] Left ventricular noncompaction. The disease is caused by mutations affecting the gene represented in this entry.

Function

[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.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Villumsen BH, Danielsen JR, Povlsen L, Sylvestersen KB, Merdes A, Beli P, Yang YG, Choudhary C, Nielsen ML, Mailand N, Bekker-Jensen S. A new cellular stress response that triggers centriolar satellite reorganization and ciliogenesis. EMBO J. 2013 Nov 27;32(23):3029-40. doi: 10.1038/emboj.2013.223. Epub 2013 Oct, 11. PMID:24121310 doi:http://dx.doi.org/10.1038/emboj.2013.223
↑ McMillan BJ, Schnute B, Ohlenhard N, Zimmerman B, Miles L, Beglova N, Klein T, Blacklow SC. A tail of two sites: a bipartite mechanism for recognition of notch ligands by mind bomb e3 ligases. Mol Cell. 2015 Mar 5;57(5):912-24. doi: 10.1016/j.molcel.2015.01.019. PMID:25747658 doi:http://dx.doi.org/10.1016/j.molcel.2015.01.019

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4xi7"

Categories: Blacklow, S C | McMillan, B J | E3 ligase | Notch signaling

@@ Line 1: / Line 1: @@
 ==Crystal structure of the MZM-REP domains of Mind bomb 1 in complex with Jagged1 N-box peptide==
 <StructureSection load='4xi7' size='340' side='right' caption='[[4xi7]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xfx|4xfx]], [[4xib|4xib]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4xi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xi7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xi7 RCSB], [http://www.ebi.ac.uk/pdbsum/4xi7 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4xi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xi7 OCA], [http://pdbe.org/4xi7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xi7 RCSB], [http://www.ebi.ac.uk/pdbsum/4xi7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xi7 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4xi7" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
 == References ==
 <references/>

4xi7

From Proteopedia

Revision as of 00:23, 26 January 2017

Crystal structure of the MZM-REP domains of Mind bomb 1 in complex with Jagged1 N-box peptide

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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