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5ohl

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Revision as of 12:23, 26 August 2020

K6-specific affimer bound to K6 diUb

Structural highlights

5ohl is a 16 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
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

Several ubiquitin chain types have remained unstudied, mainly because tools and techniques to detect these posttranslational modifications are scarce. Linkage-specific antibodies have shaped our understanding of the roles and dynamics of polyubiquitin signals but are available for only five out of eight linkage types. We here characterize K6- and K33-linkage-specific "affimer" reagents as high-affinity ubiquitin interactors. Crystal structures of affimers bound to their cognate chain types reveal mechanisms of specificity and a K11 cross-reactivity in the K33 affimer. Structure-guided improvements yield superior affinity reagents suitable for western blotting, confocal fluorescence microscopy and pull-down applications. This allowed us to identify RNF144A and RNF144B as E3 ligases that assemble K6-, K11-, and K48-linked polyubiquitin in vitro. A protocol to enrich K6-ubiquitinated proteins from cells identifies HUWE1 as a main E3 ligase for this chain type, and we show that mitofusin-2 is modified with K6-linked polyubiquitin in a HUWE1-dependent manner.

Ubiquitin Linkage-Specific Affimers Reveal Insights into K6-Linked Ubiquitin Signaling.,Michel MA, Swatek KN, Hospenthal MK, Komander D Mol Cell. 2017 Sep 20. pii: S1097-2765(17)30617-2. doi:, 10.1016/j.molcel.2017.08.020. PMID:28943312^[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
↑ Michel MA, Swatek KN, Hospenthal MK, Komander D. Ubiquitin Linkage-Specific Affimers Reveal Insights into K6-Linked Ubiquitin Signaling. Mol Cell. 2017 Sep 20. pii: S1097-2765(17)30617-2. doi:, 10.1016/j.molcel.2017.08.020. PMID:28943312 doi:http://dx.doi.org/10.1016/j.molcel.2017.08.020

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/5ohl"

@@ Line 1: / Line 1: @@
 ==K6-specific affimer bound to K6 diUb==
-<StructureSection load='5ohl' size='340' side='right' caption='[[5ohl]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+<StructureSection load='5ohl' size='340' side='right'caption='[[5ohl]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ohl]] is a 16 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OHL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OHL FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ohl]] is a 16 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OHL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5OHL FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=15P:POLYETHYLENE+GLYCOL+(N=34)'>15P</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=15P:POLYETHYLENE+GLYCOL+(N=34)'>15P</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5ohl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ohl OCA], [http://pdbe.org/5ohl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ohl RCSB], [http://www.ebi.ac.uk/pdbsum/5ohl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ohl ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ohl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ohl OCA], [http://pdbe.org/5ohl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ohl RCSB], [http://www.ebi.ac.uk/pdbsum/5ohl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ohl ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Komander, D]]
 [[Category: Michel, M A]]

5ohl

From Proteopedia

Revision as of 12:23, 26 August 2020

K6-specific affimer bound to K6 diUb

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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