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==A complex of of RNF4-RING domain, UbeV2, Ubc13-Ub (isopeptide crosslink)==
==A complex of of RNF4-RING domain, UbeV2, Ubc13-Ub (isopeptide crosslink)==
<StructureSection load='5ait' size='340' side='right' caption='[[5ait]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
<StructureSection load='5ait' size='340' side='right'caption='[[5ait]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5ait]] is a 7 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AIT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AIT FirstGlance]. <br>
<table><tr><td colspan='2'>[[5ait]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AIT 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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ait FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ait OCA], [http://pdbe.org/5ait PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ait RCSB], [http://www.ebi.ac.uk/pdbsum/5ait PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ait ProSAT]</span></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=5ait FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ait OCA], [https://pdbe.org/5ait PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ait RCSB], [https://www.ebi.ac.uk/pdbsum/5ait PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ait ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/UB2V2_HUMAN UB2V2_HUMAN]] Has no ubiquitin ligase activity on its own. The UBE2V2/UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'. This type of poly-ubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage.<ref>PMID:9705497</ref> <ref>PMID:10089880</ref> <ref>PMID:14562038</ref> <ref>PMID:20061386</ref>  [[http://www.uniprot.org/uniprot/RNF4_RAT RNF4_RAT]] E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation.<ref>PMID:9710597</ref> <ref>PMID:11319220</ref> <ref>PMID:14987998</ref> <ref>PMID:15707587</ref> <ref>PMID:18408734</ref> <ref>PMID:20943951</ref> [[http://www.uniprot.org/uniprot/UBC_BOVIN UBC_BOVIN]] Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). [[http://www.uniprot.org/uniprot/UBE2N_HUMAN UBE2N_HUMAN]] The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes (By similarity).<ref>PMID:10089880</ref> <ref>PMID:14562038</ref> <ref>PMID:19269966</ref> <ref>PMID:20061386</ref> <ref>PMID:21512573</ref> 
[https://www.uniprot.org/uniprot/RNF4_RAT RNF4_RAT] E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation.<ref>PMID:9710597</ref> <ref>PMID:11319220</ref> <ref>PMID:14987998</ref> <ref>PMID:15707587</ref> <ref>PMID:18408734</ref> <ref>PMID:20943951</ref>  
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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==See Also==
==See Also==
*[[Ubiquitin|Ubiquitin]]
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
*[[Ubiquitin conjugating enzyme|Ubiquitin conjugating enzyme]]
*[[3D structures of ubiquitin|3D structures of ubiquitin]]
*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Ubiquitin--protein ligase]]
[[Category: Bos taurus]]
[[Category: Branigan, E]]
[[Category: Homo sapiens]]
[[Category: Naismith, J H]]
[[Category: Large Structures]]
[[Category: Complex]]
[[Category: Rattus norvegicus]]
[[Category: Ligase-signaling protein complex]]
[[Category: Branigan E]]
[[Category: Naismith JH]]

Latest revision as of 14:41, 9 May 2024

A complex of of RNF4-RING domain, UbeV2, Ubc13-Ub (isopeptide crosslink)A complex of of RNF4-RING domain, UbeV2, Ubc13-Ub (isopeptide crosslink)

Structural highlights

5ait is a 7 chain structure with sequence from Bos taurus, Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.4Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RNF4_RAT E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation.[1] [2] [3] [4] [5] [6]

Publication Abstract from PubMed

RING E3 ligase-catalyzed formation of K63-linked ubiquitin chains by the Ube2V2-Ubc13 E2 complex is required in many important biological processes. Here we report the structure of the RING-domain dimer of rat RNF4 in complex with a human Ubc13 approximately Ub conjugate and Ube2V2. The structure has captured Ube2V2 bound to the acceptor (priming) ubiquitin with K63 in a position favorable for attack on the linkage between Ubc13 and the donor (second) ubiquitin held in the active 'folded back' conformation by the RING domain of RNF4. We verified the interfaces identified in the structure by in vitro ubiquitination assays of site-directed mutants. To our knowledge, this represents the first view of synthesis of K63-linked ubiquitin chains in which both substrate ubiquitin and ubiquitin-loaded E2 are juxtaposed to allow E3 ligase-mediated catalysis.

Structural basis for the RING-catalyzed synthesis of K63-linked ubiquitin chains.,Branigan E, Plechanovova A, Jaffray EG, Naismith JH, Hay RT Nat Struct Mol Biol. 2015 Jul 6. doi: 10.1038/nsmb.3052. PMID:26148049[7]

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

See Also

References

  1. ↑ Moilanen AM, Poukka H, Karvonen U, Hakli M, Janne OA, Palvimo JJ. Identification of a novel RING finger protein as a coregulator in steroid receptor-mediated gene transcription. Mol Cell Biol. 1998 Sep;18(9):5128-39. PMID:9710597
  2. ↑ Hakli M, Karvonen U, Janne OA, Palvimo JJ. The RING finger protein SNURF is a bifunctional protein possessing DNA binding activity. J Biol Chem. 2001 Jun 29;276(26):23653-60. Epub 2001 Apr 23. PMID:11319220 doi:10.1074/jbc.M009891200
  3. ↑ Hakli M, Lorick KL, Weissman AM, Janne OA, Palvimo JJ. Transcriptional coregulator SNURF (RNF4) possesses ubiquitin E3 ligase activity. FEBS Lett. 2004 Feb 27;560(1-3):56-62. PMID:14987998 doi:10.1016/S0014-5793(04)00070-5
  4. ↑ Hakli M, Karvonen U, Janne OA, Palvimo JJ. SUMO-1 promotes association of SNURF (RNF4) with PML nuclear bodies. Exp Cell Res. 2005 Mar 10;304(1):224-33. Epub 2004 Nov 23. PMID:15707587 doi:10.1016/j.yexcr.2004.10.029
  5. ↑ Tatham MH, Geoffroy MC, Shen L, Plechanovova A, Hattersley N, Jaffray EG, Palvimo JJ, Hay RT. RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat Cell Biol. 2008 May;10(5):538-46. doi: 10.1038/ncb1716. Epub 2008 Apr 13. PMID:18408734 doi:10.1038/ncb1716
  6. ↑ Geoffroy MC, Jaffray EG, Walker KJ, Hay RT. Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear bodies. Mol Biol Cell. 2010 Dec;21(23):4227-39. doi: 10.1091/mbc.E10-05-0449. Epub 2010, Oct 13. PMID:20943951 doi:10.1091/mbc.E10-05-0449
  7. ↑ Branigan E, Plechanovova A, Jaffray EG, Naismith JH, Hay RT. Structural basis for the RING-catalyzed synthesis of K63-linked ubiquitin chains. Nat Struct Mol Biol. 2015 Jul 6. doi: 10.1038/nsmb.3052. PMID:26148049 doi:http://dx.doi.org/10.1038/nsmb.3052

5ait, resolution 3.40Å

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