8v0e

From Proteopedia

(Difference between revisions)

Current revision

ANK repeat of MIB1

Structural highlights

8v0e is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.39Å
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 1 (MIB1) is a RING E3 ligase that ubiquitinates Notch ligands, a necessary step for induction of Notch signaling. The structural basis for binding of the JAG1 ligand by the N-terminal region of MIB1 is known, yet how the ankyrin (ANK) and RING domains of MIB1 cooperate to catalyze ubiquitin transfer from E2 approximately Ub to Notch ligands remains unclear. Here, we show that the third RING domain and adjacent coiled coil region (ccRING3) drive MIB1 dimerization and that MIB1 ubiquitin transfer activity relies solely on ccRING3. We report X-ray crystal structures of a UbcH5B-ccRING3 complex and the ANK domain. Directly tethering the MIB1 N-terminal region to ccRING3 forms a minimal MIB1 protein sufficient to induce a Notch response in receiver cells and rescue mib knockout phenotypes in flies. Together, these studies define the functional elements of an E3 ligase needed for ligands to induce a Notch signaling response.

Structural requirements for activity of Mind bomb1 in Notch signaling.,Cao R, Gozlan O, Airich A, Tveriakhina L, Zhou H, Jiang H, Cole PA, Aster JC, Klein T, Sprinzak D, Blacklow SC Structure. 2024 Jul 26:S0969-2126(24)00274-0. doi: 10.1016/j.str.2024.07.011. PMID:39121852^[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
↑ Cao R, Gozlan O, Airich A, Tveriakhina L, Zhou H, Jiang H, Cole PA, Aster JC, Klein T, Sprinzak D, Blacklow SC. Structural requirements for activity of Mind bomb1 in Notch signaling. Structure. 2024 Jul 26:S0969-2126(24)00274-0. PMID:39121852 doi:10.1016/j.str.2024.07.011

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/8v0e"

Categories: Homo sapiens | Large Structures | Blacklow SC | Cao R

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8v0e is ON HOLD  until Paper Publication
+==ANK repeat of MIB1==
+<StructureSection load='8v0e' size='340' side='right'caption='[[8v0e]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8v0e]] is a 3 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=8V0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8V0E 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]] 2.39&#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=8v0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8v0e OCA], [https://pdbe.org/8v0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8v0e RCSB], [https://www.ebi.ac.uk/pdbsum/8v0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8v0e 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Mind bomb 1 (MIB1) is a RING E3 ligase that ubiquitinates Notch ligands, a necessary step for induction of Notch signaling. The structural basis for binding of the JAG1 ligand by the N-terminal region of MIB1 is known, yet how the ankyrin (ANK) and RING domains of MIB1 cooperate to catalyze ubiquitin transfer from E2 approximately Ub to Notch ligands remains unclear. Here, we show that the third RING domain and adjacent coiled coil region (ccRING3) drive MIB1 dimerization and that MIB1 ubiquitin transfer activity relies solely on ccRING3. We report X-ray crystal structures of a UbcH5B-ccRING3 complex and the ANK domain. Directly tethering the MIB1 N-terminal region to ccRING3 forms a minimal MIB1 protein sufficient to induce a Notch response in receiver cells and rescue mib knockout phenotypes in flies. Together, these studies define the functional elements of an E3 ligase needed for ligands to induce a Notch signaling response.
-Authors: Cao, R., Blacklow, S.C.
+Structural requirements for activity of Mind bomb1 in Notch signaling.,Cao R, Gozlan O, Airich A, Tveriakhina L, Zhou H, Jiang H, Cole PA, Aster JC, Klein T, Sprinzak D, Blacklow SC Structure. 2024 Jul 26:S0969-2126(24)00274-0. doi: 10.1016/j.str.2024.07.011. PMID:39121852<ref>PMID:39121852</ref>
-Description: ANK repeat of MIB1
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Blacklow, S.C]]
+<div class="pdbe-citations 8v0e" style="background-color:#fffaf0;"></div>
-[[Category: Cao, R]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Blacklow SC]]
+[[Category: Cao R]]

8v0e

From Proteopedia

Current revision

ANK repeat of MIB1

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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