6dc0
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Tribbles (TRIB1) pseudokinase fused to CCAAT-enhancer binding protein (C/EBPalpha) degron== | |
| + | <StructureSection load='6dc0' size='340' side='right' caption='[[6dc0]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6dc0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DC0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DC0 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=6dc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dc0 OCA], [http://pdbe.org/6dc0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dc0 RCSB], [http://www.ebi.ac.uk/pdbsum/6dc0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dc0 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The Tribbles family of pseudokinases recruits substrates to the ubiquitin ligase COP1 to facilitate ubiquitylation. CCAAT/enhancer-binding protein (C/EBP) family transcription factors are crucial Tribbles substrates in adipocyte and myeloid cell development. We found that the TRIB1 pseudokinase was able to recruit various C/EBP family members and that the binding of C/EBPbeta was attenuated by phosphorylation. To explain the mechanism of C/EBP recruitment, we solved the crystal structure of TRIB1 in complex with C/EBPalpha, which revealed that TRIB1 underwent a substantial conformational change relative to its substrate-free structure and bound C/EBPalpha in a pseudosubstrate-like manner. Crystallographic analysis and molecular dynamics and subsequent biochemical assays showed that C/EBP binding triggered allosteric changes that link substrate recruitment to COP1 binding. These findings offer a view of pseudokinase regulation with striking parallels to bona fide kinase regulation-by means of the activation loop and alphaC helix-and raise the possibility of small molecules targeting either the activation "loop-in" or "loop-out" conformations of Tribbles pseudokinases. | ||
| - | + | Substrate binding allosterically relieves autoinhibition of the pseudokinase TRIB1.,Jamieson SA, Ruan Z, Burgess AE, Curry JR, McMillan HD, Brewster JL, Dunbier AK, Axtman AD, Kannan N, Mace PD Sci Signal. 2018 Sep 25;11(549). pii: 11/549/eaau0597. doi:, 10.1126/scisignal.aau0597. PMID:30254053<ref>PMID:30254053</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Jamieson, S | + | <div class="pdbe-citations 6dc0" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Brewster, J L]] | ||
| + | [[Category: Jamieson, S A]] | ||
| + | [[Category: Mace, P D]] | ||
| + | [[Category: Ccaat-enhancer binding protein]] | ||
| + | [[Category: Psuedokinase]] | ||
| + | [[Category: Signaling protein]] | ||
| + | [[Category: Trb1]] | ||
| + | [[Category: Tribble]] | ||
Revision as of 08:06, 10 October 2018
Tribbles (TRIB1) pseudokinase fused to CCAAT-enhancer binding protein (C/EBPalpha) degron
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