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3o65

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Revision as of 18:09, 5 August 2016

Crystal structure of a Josephin-ubiquitin complex: Evolutionary restraints on ataxin-3 deubiquitinating activity

Structural highlights

3o65 is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:	,
Gene:	ATX3L, ATXN3L, MJDL (HUMAN), UBB (HUMAN)
Activity:	Ubiquitin thiolesterase, with EC number 3.1.2.15
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ATX3L_HUMAN] Deubiquitinating enzyme that cleaves both 'Lys-48'-linked and 'Lys-63'-linked poly-ubiquitin chains (in vitro). [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.^[1] ^[2]

Publication Abstract from PubMed

The Josephin domain is a conserved cysteine protease domain found in four human deubiquitinating enzymes: ataxin-3, the ataxin-3-like protein (ATXN3L), Josephin-1, and Josephin-2. Josephin domains from these four proteins were purified and assayed for their ability to cleave ubiquitin substrates. Reaction rates differed markedly both among the different proteins and for different substrates with a given protein. The ATXN3L Josephin domain is a significantly more efficient enzyme than the ataxin-3 domain despite their sharing 85% sequence identity. To understand the structural basis of this difference, the 2.6 A x-ray crystal structure of the ATXN3L Josephin domain in complex with ubiquitin was determined. Although ataxin-3 and ATXN3L adopt similar folds, they bind ubiquitin in different, overlapping sites. Mutations were made in ataxin-3 at selected positions, introducing the corresponding ATXN3L residue. Only three such mutations are sufficient to increase the catalytic activity of the ataxin-3 domain to levels comparable with that of ATXN3L, suggesting that ataxin-3 has been subject to evolutionary restraints that keep its deubiquitinating activity in check.

Crystal Structure of a Josephin-Ubiquitin Complex: EVOLUTIONARY RESTRAINTS ON ATAXIN-3 DEUBIQUITINATING ACTIVITY.,Weeks SD, Grasty KC, Hernandez-Cuebas L, Loll PJ J Biol Chem. 2011 Feb 11;286(6):4555-65. Epub 2010 Nov 30. PMID:21118805^[3]

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

References

↑ Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A. Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell. 2006 Mar 17;21(6):737-48. PMID:16543144 doi:S1097-2765(06)00120-1
↑ Komander D. The emerging complexity of protein ubiquitination. Biochem Soc Trans. 2009 Oct;37(Pt 5):937-53. doi: 10.1042/BST0370937. PMID:19754430 doi:10.1042/BST0370937
↑ Weeks SD, Grasty KC, Hernandez-Cuebas L, Loll PJ. Crystal Structure of a Josephin-Ubiquitin Complex: EVOLUTIONARY RESTRAINTS ON ATAXIN-3 DEUBIQUITINATING ACTIVITY. J Biol Chem. 2011 Feb 11;286(6):4555-65. Epub 2010 Nov 30. PMID:21118805 doi:10.1074/jbc.M110.177360

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3o65"

@@ Line 1: / Line 1: @@
 ==Crystal structure of a Josephin-ubiquitin complex: Evolutionary restraints on ataxin-3 deubiquitinating activity==
 <StructureSection load='3o65' size='340' side='right' caption='[[3o65]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3o65]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O65 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O65 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3o65]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O65 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O65 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NEH:ETHANAMINE'>NEH</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ATX3L, ATXN3L, MJDL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), UBB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ATX3L, ATXN3L, MJDL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UBB ([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/Ubiquitin_thiolesterase Ubiquitin thiolesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.15 3.1.2.15] </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=3o65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o65 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o65 RCSB], [http://www.ebi.ac.uk/pdbsum/3o65 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=3o65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o65 OCA], [http://pdbe.org/3o65 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3o65 RCSB], [http://www.ebi.ac.uk/pdbsum/3o65 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3o65 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ 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 3o65" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 26: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Ubiquitin thiolesterase]]
 [[Category: Grasty, K C]]

3o65

From Proteopedia

Revision as of 18:09, 5 August 2016

Crystal structure of a Josephin-ubiquitin complex: Evolutionary restraints on ataxin-3 deubiquitinating activity

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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