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5oxi

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Revision as of 08:54, 27 December 2017

C-terminally retracted ubiquitin L67S mutant

Structural highlights

5oxi is a 2 chain structure with sequence from Human. 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

[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

The Ser/Thr protein kinase PINK1 phosphorylates the well-folded, globular protein ubiquitin (Ub) at a relatively protected site, Ser65. We previously showed that Ser65 phosphorylation results in a conformational change in which Ub adopts a dynamic equilibrium between the known, common Ub conformation and a distinct, second conformation wherein the last beta-strand is retracted to extend the Ser65 loop and shorten the C-terminal tail. We show using chemical exchange saturation transfer (CEST) nuclear magnetic resonance experiments that a similar, C-terminally retracted (Ub-CR) conformation also exists at low population in wild-type Ub. Point mutations in the moving beta5 and neighbouring beta-strands shift the Ub/Ub-CR equilibrium. This enabled functional studies of the two states, and we show that while the Ub-CR conformation is defective for conjugation, it demonstrates improved binding to PINK1 through its extended Ser65 loop, and is a superior PINK1 substrate. Together our data suggest that PINK1 utilises a lowly populated yet more suitable Ub-CR conformation of Ub for efficient phosphorylation. Our findings could be relevant for many kinases that phosphorylate residues in folded protein domains.

An invisible ubiquitin conformation is required for efficient phosphorylation by PINK1.,Gladkova C, Schubert AF, Wagstaff JL, Pruneda JN, Freund SMV, Komander D EMBO J. 2017 Nov 13. pii: e201797876. doi: 10.15252/embj.201797876. PMID:29133469^[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
↑ Gladkova C, Schubert AF, Wagstaff JL, Pruneda JN, Freund SMV, Komander D. An invisible ubiquitin conformation is required for efficient phosphorylation by PINK1. EMBO J. 2017 Nov 13. pii: e201797876. doi: 10.15252/embj.201797876. PMID:29133469 doi:http://dx.doi.org/10.15252/embj.201797876

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/5oxi"

@@ Line 3: / Line 3: @@
 <StructureSection load='5oxi' size='340' side='right' caption='[[5oxi]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5oxi]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OXI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OXI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5oxi]] is a 2 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=5OXI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OXI FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5oxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oxi OCA], [http://pdbe.org/5oxi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oxi RCSB], [http://www.ebi.ac.uk/pdbsum/5oxi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oxi ProSAT]</span></td></tr>
@@ Line 22: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Freund, S M.V]]
 [[Category: Gladkova, C G]]

5oxi

From Proteopedia

Revision as of 08:54, 27 December 2017

C-terminally retracted ubiquitin L67S mutant

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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