Structural insights into the recruitment of SMRT by the corepressor SHARP under phosphorylative regulation.

By Suzuka Mikami, T. Kanaba, N. Takizawa, Ayaho Kobayashi, R. Maesaki, T. Fujiwara, Yutaka Ito, M. Mishima. 2013

27 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

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In Molecular Biology

1. L. Tong
2. Gordon G. Simpson
3. K. Rataj
4. Yinglu Zhang

Citations in the corpus

• Crystal Structure of the SPOC Domain of the Arabidopsis Flowering Regulator FPA (2016, background): “Since the corresponding mutations in the SHARP SPOC domain do disrupt its recognition of unphosphorylated SMRT peptides [16], these observations may reinforce the idea that the features and functions of the FPA SPOC domain differ from those of the only other well-characterized SPOC domain.”