5cra

From Proteopedia

(Difference between revisions)

Revision as of 08:55, 4 December 2019

Structure of the SdeA DUB Domain

Structural highlights

5cra is a 4 chain structure with sequence from Atcc 33152 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	5crb, 5crc
Gene:	UBB (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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

Manipulation of the host's ubiquitin network is emerging as an important strategy for counteracting and repurposing the posttranslational modification machineries of the host by pathogens. Ubiquitin E3 ligases encoded by infectious agents are well known, as are a variety of viral deubiquitinases (DUBs). Bacterial DUBs have been discovered, but little is known about the structure and mechanism underlying their ubiquitin recognition. In this report, we found that members of the Legionella pneumophila SidE effector family harbor a DUB module important for ubiquitin dynamics on the bacterial phagosome. Structural analysis of this domain alone and in complex with ubiquitin vinyl methyl ester (Ub-VME) reveals unique molecular contacts used in ubiquitin recognition. Instead of relying on the Ile44 patch of ubiquitin, as commonly used in eukaryotic counterparts, the SdeADub module engages Gln40 of ubiquitin. The architecture of the active-site cleft presents an open arrangement with conformational plasticity, permitting deubiquitination of three of the most abundant polyubiquitin chains, with a distinct preference for Lys63 linkages. We have shown that this preference enables efficient removal of Lys63 linkages from the phagosomal surface. Remarkably, the structure reveals by far the most parsimonious use of molecular contacts to achieve deubiquitination, with less than 1,000 A2 of accessible surface area buried upon complex formation with ubiquitin. This type of molecular recognition appears to enable dual specificity toward ubiquitin and the ubiquitin-like modifier NEDD8.

Structural basis of substrate recognition by a bacterial deubiquitinase important for dynamics of phagosome ubiquitination.,Sheedlo MJ, Qiu J, Tan Y, Paul LN, Luo ZQ, Das C Proc Natl Acad Sci U S A. 2015 Nov 23. pii: 201514568. PMID:26598703^[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
↑ Sheedlo MJ, Qiu J, Tan Y, Paul LN, Luo ZQ, Das C. Structural basis of substrate recognition by a bacterial deubiquitinase important for dynamics of phagosome ubiquitination. Proc Natl Acad Sci U S A. 2015 Nov 23. pii: 201514568. PMID:26598703 doi:http://dx.doi.org/10.1073/pnas.1514568112

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/5cra"

@@ Line 1: / Line 1: @@
 ==Structure of the SdeA DUB Domain==
-<StructureSection load='5cra' size='340' side='right' caption='[[5cra]], [[Resolution|resolution]] 2.64&Aring;' scene=''>
+<StructureSection load='5cra' size='340' side='right'caption='[[5cra]], [[Resolution|resolution]] 2.64&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5cra]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CRA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CRA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5cra]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_33152 Atcc 33152] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CRA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CRA FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GVE:METHYL+4-AMINOBUTANOATE'>GVE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5crb|5crb]], [[5crc|5crc]]</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=5cra FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cra OCA], [http://pdbe.org/5cra PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cra RCSB], [http://www.ebi.ac.uk/pdbsum/5cra PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5cra FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cra OCA], [http://pdbe.org/5cra PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cra RCSB], [http://www.ebi.ac.uk/pdbsum/5cra PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cra ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Atcc 33152]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Das, C]]
 [[Category: Luo, Z Q]]

5cra

From Proteopedia

Revision as of 08:55, 4 December 2019

Structure of the SdeA DUB Domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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