6DC0
Tribbles (TRIB1) pseudokinase fused to CCAAT-enhancer binding protein (C/EBPalpha) degron
Summary for 6DC0
| Entry DOI | 10.2210/pdb6dc0/pdb |
| Descriptor | Tribbles homolog 1,CCAAT/enhancer-binding protein alpha (2 entities in total) |
| Functional Keywords | tribbles, psuedokinase, ccaat-enhancer binding protein, trb1, signaling protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 65618.95 |
| Authors | Jamieson, S.A.,Brewster, J.L.,Mace, P.D. (deposition date: 2018-05-03, release date: 2018-10-10, Last modification date: 2023-10-04) |
| Primary citation | Jamieson, S.A.,Ruan, Z.,Burgess, A.E.,Curry, J.R.,McMillan, H.D.,Brewster, J.L.,Dunbier, A.K.,Axtman, A.D.,Kannan, N.,Mace, P.D. Substrate binding allosterically relieves autoinhibition of the pseudokinase TRIB1. Sci Signal, 11:-, 2018 Cited by PubMed Abstract: 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/EBPβ was attenuated by phosphorylation. To explain the mechanism of C/EBP recruitment, we solved the crystal structure of TRIB1 in complex with C/EBPα, which revealed that TRIB1 underwent a substantial conformational change relative to its substrate-free structure and bound C/EBPα 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 αC helix-and raise the possibility of small molecules targeting either the activation "loop-in" or "loop-out" conformations of Tribbles pseudokinases. PubMed: 30254053DOI: 10.1126/scisignal.aau0597 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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