|
|
| (4 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Crystal Structure of mUCH37-hRPN13 CTD-hUb complex== | | ==Crystal Structure of mUCH37-hRPN13 CTD-hUb complex== |
| - | <StructureSection load='4wlr' size='340' side='right' caption='[[4wlr]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4wlr' size='340' side='right'caption='[[4wlr]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4wlr]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WLR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WLR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4wlr]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WLR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WLR FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wlp|4wlp]], [[4wlq|4wlq]]</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]] 1.997Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </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=4wlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wlr OCA], [https://pdbe.org/4wlr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wlr RCSB], [https://www.ebi.ac.uk/pdbsum/4wlr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wlr ProSAT]</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=4wlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wlr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wlr RCSB], [http://www.ebi.ac.uk/pdbsum/4wlr PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UCHL5_MOUSE UCHL5_MOUSE]] Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1 (By similarity). [[http://www.uniprot.org/uniprot/UBB_HUMAN UBB_HUMAN]] 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.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref> [[http://www.uniprot.org/uniprot/ADRM1_HUMAN ADRM1_HUMAN]] Functions as a proteasomal ubiquitin receptor. Recruits the deubiquitinating enzyme UCHL5 at the 26S proteasome and promotes its activity.<ref>PMID:16990800</ref> <ref>PMID:17139257</ref> <ref>PMID:16815440</ref> <ref>PMID:16906146</ref> <ref>PMID:18497817</ref> | + | [https://www.uniprot.org/uniprot/UCHL5_MOUSE UCHL5_MOUSE] Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1 (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 17: |
Line 17: |
| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4wlr" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Thioesterase 3D structures|Thioesterase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ubiquitinyl hydrolase 1]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Hemmis, C W]] | + | [[Category: Large Structures]] |
| - | [[Category: Hill, C P]] | + | [[Category: Mus musculus]] |
| - | [[Category: VanderLinden, R]] | + | [[Category: Hemmis CW]] |
| - | [[Category: Whitby, F G]] | + | [[Category: Hill CP]] |
| - | [[Category: Protein binding]] | + | [[Category: VanderLinden R]] |
| - | [[Category: Uch37 rpn13 proteasome ino80 dub]] | + | [[Category: Whitby FG]] |
| Structural highlights
Function
UCHL5_MOUSE Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1 (By similarity).
Publication Abstract from PubMed
The UCH37 deubiquitylase functions in two large and very different complexes, the 26S proteasome and the INO80 chromatin remodeler. We have performed biochemical characterization and determined crystal structures of UCH37 in complexes with RPN13 and NFRKB, which mediate its recruitment to the proteasome and INO80, respectively. RPN13 and NFRKB make similar contacts to the UCH37 C-terminal domain but quite different contacts to the catalytic UCH domain. RPN13 can activate UCH37 by disrupting dimerization, although physiologically relevant activation likely results from stabilization of a surface competent for ubiquitin binding and modulation of the active-site crossover loop. In contrast, NFRKB inhibits UCH37 by blocking the ubiquitin-binding site and by disrupting the enzyme active site. These findings reveal remarkable commonality in mechanisms of recruitment, yet very different mechanisms of regulating enzyme activity, and provide a foundation for understanding the roles of UCH37 in the unrelated proteasome and INO80 complexes.
Structural Basis for the Activation and Inhibition of the UCH37 Deubiquitylase.,VanderLinden RT, Hemmis CW, Schmitt B, Ndoja A, Whitby FG, Robinson H, Cohen RE, Yao T, Hill CP Mol Cell. 2015 Mar 5;57(5):901-11. doi: 10.1016/j.molcel.2015.01.016. Epub 2015, Feb 19. PMID:25702872[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ VanderLinden RT, Hemmis CW, Schmitt B, Ndoja A, Whitby FG, Robinson H, Cohen RE, Yao T, Hill CP. Structural Basis for the Activation and Inhibition of the UCH37 Deubiquitylase. Mol Cell. 2015 Mar 5;57(5):901-11. doi: 10.1016/j.molcel.2015.01.016. Epub 2015, Feb 19. PMID:25702872 doi:http://dx.doi.org/10.1016/j.molcel.2015.01.016
|
