On 4th January 2018, a paper has been published from Nucleic Acids Research (IF=10.162) by the research team of Dr. Kota Kasahara (Ritsumeikan University), Dr. Masaaki Shiina, Prof. Kazuhiro Ogata (Yokohama City University), Prof. Junichi Higo and Prof. Haruki Nakamura (IPR, Osaka University), revealing the regulation mechanism of the intrinsically disordered region of Ets1 transcription factor due to phosphorylation of Ser residues by molecular simulation and biochemical studies.
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Multi-modal interactions are frequently observed in intrinsically disordered regions (IDRs) of proteins upon binding to their partners. In many cases, posttranslational modifications in IDRs are accompanied by coupled folding and binding. From both molecular simulations and biochemical experiments with mutational studies, we show that the IDR including a Ser rich region (SRR) of the transcription factor Ets1, just before the DNA-binding core domain, undergoes multi-modal interactions when the SRR is not phosphorylated. In the phosphorylated state, the SRR forms a few specific complex structures with the Ets1 core, covering the recognition helix in the core and drastically reducing the DNA binding affinities as the auto-inhibitory state. The binding kinetics of mutated Ets1 indicates that aromatic residues in the SRR can be substituted with other hydrophobic residues for the interactions with the Ets1 core.