2n2k

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Revision as of 15:57, 16 November 2017

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Ensemble structure of the closed state of Lys63-linked diubiquitin in the absence of a ligand

Structural highlights

2n2k is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1ubq, 3h7p
Gene:	UBC (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Warning: this is a large structure, and loading might take a long time or not happen at all.

Function

[UBC_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

A polyubiquitin comprises multiple covalently linked ubiquitins and recognizes myriad targets. Free or bound to ligands, a polyubiquitin is found in different arrangements of ubiquitin subunits. To understand the structural basis for polyubiquitin quaternary plasticity and to explore the target recognition mechanism, we characterize the conformational space of Lys63-linked diubiquitin (K63-Ub2). Refining against inter-subunit paramagnetic NMR data, we show that free K63-Ub2 exists as a dynamic ensemble comprising multiple closed and open quaternary states. The quaternary dynamics enables K63-Ub2 to be specifically recognized in a variety of signaling pathways. When binding to a target protein, one of the preexisting quaternary states is selected and stabilized. A point mutation that shifts the equilibrium between the different states modulates the binding affinities towards K63-Ub2 ligands. This conformational selection mechanism at quaternary level may be used by polyubiquitins of different lengths and linkages for target recognition.

Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition.,Liu Z, Gong Z, Jiang WX, Yang J, Zhu WK, Guo DC, Zhang WP, Liu ML, Tang C Elife. 2015 Jun 19;4. doi: 10.7554/eLife.05767. PMID:26090905^[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
↑ Liu Z, Gong Z, Jiang WX, Yang J, Zhu WK, Guo DC, Zhang WP, Liu ML, Tang C. Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition. Elife. 2015 Jun 19;4. doi: 10.7554/eLife.05767. PMID:26090905 doi:http://dx.doi.org/10.7554/eLife.05767

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/2n2k"

@@ Line 1: / Line 1: @@
+{{Large structure}}
 ==Ensemble structure of the closed state of Lys63-linked diubiquitin in the absence of a ligand==
 <StructureSection load='2n2k' size='340' side='right' caption='[[2n2k]], [[NMR_Ensembles_of_Models | 70 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2n2k]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N2K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2n2k]] is a 2 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=2N2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N2K FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTN:S-[(1-OXYL-2,2,5,5-TETRAMETHYL-2,5-DIHYDRO-1H-PYRROL-3-YL)METHYL]+METHANESULFONOTHIOATE'>MTN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ubq|1ubq]], [[3h7p|3h7p]]</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=2n2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n2k OCA], [http://pdbe.org/2n2k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n2k RCSB], [http://www.ebi.ac.uk/pdbsum/2n2k PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBC ([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=2n2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n2k OCA], [http://pdbe.org/2n2k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n2k RCSB], [http://www.ebi.ac.uk/pdbsum/2n2k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n2k ProSAT]</span></td></tr>
 </table>
 {{Large structure}}
@@ Line 23: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Gong, Z]]
 [[Category: Liu, Z]]

2n2k

From Proteopedia

Revision as of 15:57, 16 November 2017

Ensemble structure of the closed state of Lys63-linked diubiquitin in the absence of a ligand

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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