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| | <StructureSection load='4un2' size='340' side='right'caption='[[4un2]], [[Resolution|resolution]] 1.51Å' scene=''> | | <StructureSection load='4un2' size='340' side='right'caption='[[4un2]], [[Resolution|resolution]] 1.51Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4un2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UN2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UN2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4un2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UN2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UN2 FirstGlance]. <br> |
| - | </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=4un2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4un2 OCA], [http://pdbe.org/4un2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4un2 RCSB], [http://www.ebi.ac.uk/pdbsum/4un2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4un2 ProSAT]</span></td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4un2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4un2 OCA], [https://pdbe.org/4un2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4un2 RCSB], [https://www.ebi.ac.uk/pdbsum/4un2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4un2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UBC_HUMAN 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.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref> [[http://www.uniprot.org/uniprot/DSK2_YEAST DSK2_YEAST]] Involved, with RAD23 in spindle pole body duplication. Involved in the ubiquitin-proteasome proteolytic pathway. | + | [https://www.uniprot.org/uniprot/UBC_HUMAN 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.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ubiquitin|Ubiquitin]] | + | *[[3D structures of ubiquitin|3D structures of ubiquitin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 18824]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ban, D]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Becker, S]] | + | [[Category: Ban D]] |
| - | [[Category: Giller, K]] | + | [[Category: Becker S]] |
| - | [[Category: Griesinger, C]] | + | [[Category: Giller K]] |
| - | [[Category: Groot, B L.de]]
| + | [[Category: Griesinger C]] |
| - | [[Category: Lee, D]] | + | [[Category: Lee D]] |
| - | [[Category: Michielssens, S]] | + | [[Category: Michielssens S]] |
| - | [[Category: Peters, J H]] | + | [[Category: Peters JH]] |
| - | [[Category: Pratihar, S]] | + | [[Category: Pratihar S]] |
| - | [[Category: Sabo, T M]] | + | [[Category: Sabo TM]] |
| - | [[Category: Seeliger, D]] | + | [[Category: Seeliger D]] |
| - | [[Category: Sharma, M]] | + | [[Category: Sharma M]] |
| - | [[Category: Protein binding]] | + | [[Category: De Groot BL]] |
| - | [[Category: Protein degradation]]
| + | |
| - | [[Category: Ubiquitin-associated domain]]
| + | |
| Structural highlights
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
In a conformational selection scenario, manipulating the populations of binding-competent states should be expected to affect protein binding. We demonstrate how in silico designed point mutations within the core of ubiquitin, remote from the binding interface, change the binding specificity by shifting the conformational equilibrium of the ground-state ensemble between open and closed substates that have a similar population in the wild-type protein. Binding affinities determined by NMR titration experiments agree with the predictions, thereby showing that, indeed, a shift in the conformational equilibrium enables us to alter ubiquitin's binding specificity and hence its function. Thus, we present a novel route towards designing specific binding by a conformational shift through exploiting the fact that conformational selection depends on the concentration of binding-competent substates.
A Designed Conformational Shift To Control Protein Binding Specificity.,Michielssens S, Peters JH, Ban D, Pratihar S, Seeliger D, Sharma M, Giller K, Sabo TM, Becker S, Lee D, Griesinger C, de Groot BL Angew Chem Int Ed Engl. 2014 Aug 12. doi: 10.1002/anie.201403102. PMID:25115701[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Michielssens S, Peters JH, Ban D, Pratihar S, Seeliger D, Sharma M, Giller K, Sabo TM, Becker S, Lee D, Griesinger C, de Groot BL. A Designed Conformational Shift To Control Protein Binding Specificity. Angew Chem Int Ed Engl. 2014 Aug 12. doi: 10.1002/anie.201403102. PMID:25115701 doi:http://dx.doi.org/10.1002/anie.201403102
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