Journal article
Molecular Mechanism of CCAAT-Enhancer Binding Protein Recruitment by the TRIB1 Pseudokinase
James M Murphy, Yoshio Nakatani, Sam A Jamieson, Weiwen Dai, Isabelle S Lucet, Peter D Mace
STRUCTURE | CELL PRESS | Published : 2015
Abstract
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 αC 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 αC helix. In addition, we have identified a..
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Awarded by Victorian State Government Operational Infrastructure Support, NHMRC IRIISS grant
Funding Acknowledgements
This work was supported by the Health Research Council of New Zealand and a Rutherford Discovery Fellowship from the New Zealand government administered by the Royal Society of New Zealand (to P.D.M.). Additional support was provided by the Australian Cancer Research Foundation (I.S.L., W.D.) and the Victorian State Government Operational Infrastructure Support, NHMRC IRIISS grant (9000220; to J.M.M. and I.S.L.). This research was undertaken on both the Macromolecular crystallography (MX1 and MX2), and smallangle X-ray scattering beamlines at the Australian Synchrotron, VIC, Australia. We thank the New Zealand synchrotron group for facilitating access to the MX beamlines, and Dr. Abhishek Kumar for technical assistance.