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| | ==Pseudokinase and C-terminal extension of Human Tribbles Homolog 1== | | ==Pseudokinase and C-terminal extension of Human Tribbles Homolog 1== |
| - | <StructureSection load='5cem' size='340' side='right' caption='[[5cem]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='5cem' size='340' side='right'caption='[[5cem]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5cem]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CEM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CEM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5cem]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CEM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CEM 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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cek|5cek]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=5cem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cem OCA], [http://pdbe.org/5cem PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cem RCSB], [http://www.ebi.ac.uk/pdbsum/5cem PDBsum]</span></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=5cem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cem OCA], [https://pdbe.org/5cem PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cem RCSB], [https://www.ebi.ac.uk/pdbsum/5cem PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cem ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TRIB1_HUMAN TRIB1_HUMAN]] Interacts with MAPK kinases and regulates activation of MAP kinases. May not display kinase activity.<ref>PMID:15299019</ref> <ref>PMID:15299019</ref> | + | [https://www.uniprot.org/uniprot/TRIB1_HUMAN TRIB1_HUMAN] Interacts with MAPK kinases and regulates activation of MAP kinases. May not display kinase activity.<ref>PMID:15299019</ref> <ref>PMID:15299019</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | CCAAT-enhancer binding proteins (C/EBPs) are transcription factors that play a central role in the differentiation of myeloid cells and adipocytes. Tribbles pseudokinases govern levels of C/EBPs by recruiting them to the COP1 ubiquitin ligase for ubiquitination. Here, we present the first crystal structure of a Tribbles protein, which reveals a catalytically inactive TRIB1 pseudokinase domain with a unique adaptation in the alphaC helix. A second crystal structure and biophysical studies of TRIB1 with its C-terminal extension, which includes the COP1-binding motif, show that the C-terminal extension is sequestered at a site formed by the modified TRIB1 alphaC helix. In addition, we have identified and characterized the TRIB1 substrate-recognition sequence within C/EBPalpha, which is evolutionarily conserved in C/EBP transcription factors. Binding studies indicate that C/EBPalpha recruitment is weaker in the presence of the C-terminal COP1-binding motif, but the magnitude of this effect suggests that the two bind distinct rather directly overlapping binding sites.
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| - | Molecular Mechanism of CCAAT-Enhancer Binding Protein Recruitment by the TRIB1 Pseudokinase.,Murphy JM, Nakatani Y, Jamieson SA, Dai W, Lucet IS, Mace PD Structure. 2015 Nov 3;23(11):2111-21. doi: 10.1016/j.str.2015.08.017. Epub 2015, Oct 9. PMID:26455797<ref>PMID:26455797</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5cem" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Mace, P D]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Nakatani, Y]] | + | [[Category: Large Structures]] |
| - | [[Category: Kinase]] | + | [[Category: Mace PD]] |
| - | [[Category: Kinase-like]] | + | [[Category: Nakatani Y]] |
| - | [[Category: Transferase]]
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| Structural highlights
Function
TRIB1_HUMAN Interacts with MAPK kinases and regulates activation of MAP kinases. May not display kinase activity.[1] [2]
References
- ↑ Kiss-Toth E, Bagstaff SM, Sung HY, Jozsa V, Dempsey C, Caunt JC, Oxley KM, Wyllie DH, Polgar T, Harte M, O'neill LA, Qwarnstrom EE, Dower SK. Human tribbles, a protein family controlling mitogen-activated protein kinase cascades. J Biol Chem. 2004 Oct 8;279(41):42703-8. Epub 2004 Aug 6. PMID:15299019 doi:http://dx.doi.org/10.1074/jbc.M407732200
- ↑ Kiss-Toth E, Bagstaff SM, Sung HY, Jozsa V, Dempsey C, Caunt JC, Oxley KM, Wyllie DH, Polgar T, Harte M, O'neill LA, Qwarnstrom EE, Dower SK. Human tribbles, a protein family controlling mitogen-activated protein kinase cascades. J Biol Chem. 2004 Oct 8;279(41):42703-8. Epub 2004 Aug 6. PMID:15299019 doi:http://dx.doi.org/10.1074/jbc.M407732200
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