6k2k

From Proteopedia

(Difference between revisions)

Revision as of 06:57, 31 July 2019

Solution structure of MUL1-RING domain

Structural highlights

6k2k is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	MUL1, C1orf166, GIDE, MAPL, MULAN, RNF218 (HUMAN)
Activity:	RING-type E3 ubiquitin transferase, with EC number 2.3.2.27
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MUL1_HUMAN] Exhibits weak E3 ubiquitin-protein ligase activity (PubMed:18591963, PubMed:19407830, PubMed:22410793). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates (PubMed:18591963, PubMed:19407830, PubMed:22410793). Can ubiquitinate AKT1 preferentially at 'Lys-284' involving 'Lys-48'-linked polyubiquitination and seems to be involved in regulation of Akt signaling by targeting phosphorylated Akt to proteosomal degradation (PubMed:22410793). Proposed to preferentially act as a SUMO E3 ligase at physiological concentrations (PubMed:19407830). Plays a role in the control of mitochondrial morphology by promoting mitochondrial fragmentation, and influences mitochondrial localization (PubMed:19407830, PubMed:18207745, PubMed:18213395). Likely to promote mitochondrial fission through negatively regulating the mitochondrial fusion proteins MFN1 and MFN2, acting in a pathway that is parallel to the PRKN/PINK1 regulatory pathway (PubMed:24898855). May also be involved in the sumoylation of the membrane fission protein DNM1L (PubMed:18207745, PubMed:19407830). Inhibits cell growth (PubMed:18591963, PubMed:22410793). When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis (PubMed:23399697). Involved in the modulation of innate immune defense against viruses by inhibiting DDX58-dependent antiviral response (PubMed:23399697). Can mediate DDX58 sumoylation and disrupt its polyubiquitination (PubMed:23399697).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

Mitochondrial E3 ubiquitin ligase 1 (MUL1) is a multifunctional mitochondrial protein involved in various biological processes such as mitochondrial dynamics, cell growth, apoptosis, and mitophagy. MUL1 mediates the ubiquitylation of mitochondrial p53 for proteasomal degradation. Although the interaction of MUL1-RING domain with its substrate, p53, is a unique mechanism in RING-mediated ubiquitylation, the molecular basis of this process remains unknown. In this study, we determined the solution structure of the MUL1-RING domain and characterized its interaction with the p53 transactivation domain (p53-TAD) by nuclear magnetic resonance (NMR) spectroscopy. The overall structure of the MUL1-RING domain is similar to those of RING domains of other E3 ubiquitinases. The MUL1-RING domain adopts a betabetaalphabeta fold with three anti-parallel beta-strands and one alpha-helix, containing a canonical cross-brace motif for the ligation of two zinc ions. Through NMR chemical shift perturbation experiments, we determined the p53-TAD-binding site in the MUL1-RING domain and showed that the MUL1-RING domain interacts mainly with the p53-TAD2 subdomain composed of residues 39-57. Taken together, our results provide a molecular basis for the novel recognition mechanism of the p53-TAD substrate by the MUL1-RING domain.

Solution structure of MUL1-RING domain and its interaction with p53 transactivation domain.,Lee MS, Lee SO, Lee MK, Yi GS, Lee CK, Ryu KS, Chi SW Biochem Biophys Res Commun. 2019 Jun 21. pii: S0006-291X(19)31237-9. doi:, 10.1016/j.bbrc.2019.06.101. PMID:31235254^[8]

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

References

↑ Neuspiel M, Schauss AC, Braschi E, Zunino R, Rippstein P, Rachubinski RA, Andrade-Navarro MA, McBride HM. Cargo-selected transport from the mitochondria to peroxisomes is mediated by vesicular carriers. Curr Biol. 2008 Jan 22;18(2):102-8. PMID:18207745 doi:http://dx.doi.org/S0960-9822(07)02435-9
↑ Li W, Bengtson MH, Ulbrich A, Matsuda A, Reddy VA, Orth A, Chanda SK, Batalov S, Joazeiro CA. Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling. PLoS One. 2008 Jan 23;3(1):e1487. doi: 10.1371/journal.pone.0001487. PMID:18213395 doi:http://dx.doi.org/10.1371/journal.pone.0001487
↑ Zhang B, Huang J, Li HL, Liu T, Wang YY, Waterman P, Mao AP, Xu LG, Zhai Z, Liu D, Marrack P, Shu HB. GIDE is a mitochondrial E3 ubiquitin ligase that induces apoptosis and slows growth. Cell Res. 2008 Sep;18(9):900-10. PMID:18591963 doi:http://dx.doi.org/cr200875
↑ Braschi E, Zunino R, McBride HM. MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission. EMBO Rep. 2009 Jul;10(7):748-54. Epub 2009 May 1. PMID:19407830 doi:http://dx.doi.org/embor200986
↑ Bae S, Kim SY, Jung JH, Yoon Y, Cha HJ, Lee H, Kim K, Kim J, An IS, Kim J, Um HD, Park IC, Lee SJ, Nam SY, Jin YW, Lee JH, An S. Akt is negatively regulated by the MULAN E3 ligase. Cell Res. 2012 May;22(5):873-85. doi: 10.1038/cr.2012.38. Epub 2012 Mar 13. PMID:22410793 doi:http://dx.doi.org/10.1038/cr.2012.38
↑ Jenkins K, Khoo JJ, Sadler A, Piganis R, Wang D, Borg NA, Hjerrild K, Gould J, Thomas BJ, Nagley P, Hertzog PJ, Mansell A. Mitochondrially localised MUL1 is a novel modulator of antiviral signaling. Immunol Cell Biol. 2013 Apr;91(4):321-30. doi: 10.1038/icb.2013.7. Epub 2013 Feb , 12. PMID:23399697 doi:http://dx.doi.org/10.1038/icb.2013.7
↑ Yun J, Puri R, Yang H, Lizzio MA, Wu C, Sheng ZH, Guo M. MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin. Elife. 2014 Jun 4;3:e01958. doi: 10.7554/eLife.01958. PMID:24898855 doi:http://dx.doi.org/10.7554/eLife.01958
↑ Lee MS, Lee SO, Lee MK, Yi GS, Lee CK, Ryu KS, Chi SW. Solution structure of MUL1-RING domain and its interaction with p53 transactivation domain. Biochem Biophys Res Commun. 2019 Jun 21. pii: S0006-291X(19)31237-9. doi:, 10.1016/j.bbrc.2019.06.101. PMID:31235254 doi:http://dx.doi.org/10.1016/j.bbrc.2019.06.101

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6k2k"

@@ Line 3: / Line 3: @@
 <StructureSection load='6k2k' size='340' side='right'caption='[[6k2k]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6k2k]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6K2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6K2K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6k2k]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6K2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6K2K FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MUL1, C1orf166, GIDE, MAPL, MULAN, RNF218 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </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=6k2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6k2k OCA], [http://pdbe.org/6k2k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6k2k RCSB], [http://www.ebi.ac.uk/pdbsum/6k2k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6k2k ProSAT]</span></td></tr>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: RING-type E3 ubiquitin transferase]]

6k2k

From Proteopedia

Revision as of 06:57, 31 July 2019

Solution structure of MUL1-RING domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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