Phosphorylation of an intrinsically disordered region of Ets1 shifts a multi-modal interaction ensemble to an auto-inhibitory state.

Abstract:

:Multi-modal interactions are frequently observed in intrinsically disordered regions (IDRs) of proteins upon binding to their partners. In many cases, post-translational 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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Kasahara K,Shiina M,Higo J,Ogata K,Nakamura H

doi

10.1093/nar/gkx1297

subject

Has Abstract

pub_date

2018-03-16 00:00:00

pages

2243-2251

issue

5

eissn

0305-1048

issn

1362-4962

pii

4788344

journal_volume

46

pub_type

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