2RT5

Structural insights into the recruitment of SMRT by the co-repressor SHARP under phosphorylative regulation

2RT5 の概要

• エントリーDOI: 10.2210/pdb2rt5/pdb
• NMR情報: BMRB: 11504
• 分子名称: Msx2-interacting protein, peptide from Silencing mediator of retinoic acid and thyroid hormone receptor (2 entities in total)
• 機能のキーワード: sharp, spoc domain, smrt, phosphorylation, transcription regulator
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q96T58 Q9Y618
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 19574.28

構造登録者

Mikami, S.,Kanaba, T.,Mishima, M. (登録日: 2013-04-22, 公開日: 2013-12-04, 最終更新日: 2024-11-20)

主引用文献

Mikami, S.,Kanaba, T.,Takizawa, N.,Kobayashi, A.,Maesaki, R.,Fujiwara, T.,Ito, Y.,Mishima, M.
Structural insights into the recruitment of SMRT by the corepressor SHARP under phosphorylative regulation.
Structure, 22:35-46, 2014

PubMed Abstract: The transcriptional corepressors SMRT/NCoR, components of histone deacetylase complexes, interact with nuclear receptors and many other transcription factors. SMRT is a target for the ubiquitously expressed protein kinase CK2, which is known to phosphorylate a wide variety of substrates. Increasing evidence suggests that CK2 plays a regulatory role in many cellular events, particularly, in transcription. However, little is known about the precise mode of action involved. Here, we report the three-dimensional structure of a SMRT/HDAC1-associated repressor protein (SHARP) in complex with phosphorylated SMRT, as determined by solution NMR. Phosphorylation of the CK2 site on SMRT significantly increased affinity for SHARP. We also confirmed the significance of CK2 phosphorylation by reporter assay and propose a mechanism involving the process of phosphorylation acting as a molecular switch. Finally, we propose that the SPOC domain functions as a phosphorylation binding module.

PubMed: 24268649
DOI: 10.1016/j.str.2013.10.007

実験手法

SOLUTION NMR