5CEM

Pseudokinase and C-terminal extension of Human Tribbles Homolog 1

5CEM の概要

• エントリーDOI: 10.2210/pdb5cem/pdb
• 関連するPDBエントリー: 5CEK
• 分子名称: Tribbles homolog 1, SULFATE ION (3 entities in total)
• 機能のキーワード: kinase, kinase-like, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33548.08

構造登録者

Mace, P.D.,Nakatani, Y. (登録日: 2015-07-07, 公開日: 2015-11-11, 最終更新日: 2024-03-06)

主引用文献

Murphy, J.M.,Nakatani, Y.,Jamieson, S.A.,Dai, W.,Lucet, I.S.,Mace, P.D.
Molecular Mechanism of CCAAT-Enhancer Binding Protein Recruitment by the TRIB1 Pseudokinase.
Structure, 23:2111-2121, 2015

PubMed 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 and characterized the TRIB1 substrate-recognition sequence within C/EBPα, which is evolutionarily conserved in C/EBP transcription factors. Binding studies indicate that C/EBPα 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.

PubMed: 26455797
DOI: 10.1016/j.str.2015.08.017

実験手法

X-RAY DIFFRACTION (2.1 Å)