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| | ==Solution structure of human ubiquitin with three alanine mutations in living eukaryotic cells by in-cell NMR spectroscopy== | | ==Solution structure of human ubiquitin with three alanine mutations in living eukaryotic cells by in-cell NMR spectroscopy== |
| - | <StructureSection load='5zd0' size='340' side='right'caption='[[5zd0]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='5zd0' size='340' side='right'caption='[[5zd0]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5zd0]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZD0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZD0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5zd0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZD0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZD0 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=5zd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zd0 OCA], [http://pdbe.org/5zd0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zd0 RCSB], [http://www.ebi.ac.uk/pdbsum/5zd0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zd0 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=5zd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zd0 OCA], [https://pdbe.org/5zd0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zd0 RCSB], [https://www.ebi.ac.uk/pdbsum/5zd0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zd0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UBB_HUMAN 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.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref> | + | [https://www.uniprot.org/uniprot/UBB_HUMAN 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.<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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| | </div> | | </div> |
| | <div class="pdbe-citations 5zd0" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5zd0" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[3D structures of ubiquitin|3D structures of ubiquitin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Guentert, P]] | + | [[Category: Guentert P]] |
| - | [[Category: Ikeya, T]] | + | [[Category: Ikeya T]] |
| - | [[Category: Ito, Y]] | + | [[Category: Ito Y]] |
| - | [[Category: Kamoshida, H]] | + | [[Category: Kamoshida H]] |
| - | [[Category: Mishima, M]] | + | [[Category: Mishima M]] |
| - | [[Category: Shirakawa, M]] | + | [[Category: Shirakawa M]] |
| - | [[Category: Tanaka, T]] | + | [[Category: Tanaka T]] |
| - | [[Category: Cytosolic protein]]
| + | |
| - | [[Category: Regulatory protein]]
| + | |
| - | [[Category: Ubiquitination]]
| + | |
| Structural highlights
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
Proteins in living cells interact specifically or nonspecifically with an enormous number of biomolecules. To understand the behavior of proteins under intracellular crowding conditions, it is indispensable to observe their three-dimensional (3D) structures at the atomic level in a physiologically natural environment. We demonstrate the first de novo protein structure determinations in eukaryotes with the sf9 cell/baculovirus system using NMR data from living cells exclusively. The method was applied to five proteins, rat calmodulin, human HRas, human ubiquitin, T. thermophilus HB8 TTHA1718, and Streptococcus protein G B1 domain. In all cases, we could obtain structural information from well-resolved in-cell 3D nuclear Overhauser effect spectroscopy (NOESY) data, suggesting that our method can be a standard tool for protein structure determinations in living eukaryotic cells. For three proteins, we achieved well-converged 3D structures. Among these, the in-cell structure of protein G B1 domain was most accurately determined, demonstrating that a helix-loop region is tilted away from a beta-sheet compared to the conformation in diluted solution.
High-Resolution Protein 3D Structure Determination in Living Eukaryotic Cells.,Tanaka T, Ikeya T, Kamoshida H, Suemoto Y, Mishima M, Shirakawa M, Guntert P, Ito Y Angew Chem Int Ed Engl. 2019 May 27;58(22):7284-7288. doi:, 10.1002/anie.201900840. Epub 2019 Apr 25. PMID:30938016[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
- ↑ Tanaka T, Ikeya T, Kamoshida H, Suemoto Y, Mishima M, Shirakawa M, Guntert P, Ito Y. High-Resolution Protein 3D Structure Determination in Living Eukaryotic Cells. Angew Chem Int Ed Engl. 2019 May 27;58(22):7284-7288. doi:, 10.1002/anie.201900840. Epub 2019 Apr 25. PMID:30938016 doi:http://dx.doi.org/10.1002/anie.201900840
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