Structural Characterization of the SMRT Corepressor Interacting with Histone Deacetylase 7.

Abstract : The 2525 amino acid SMRT corepressor is an intrinsically disordered hub protein responsible for binding and coordinating the activities of multiple transcription factors and chromatin modifying enzymes. Here we have studied its interaction with HDAC7, a class IIa deacetylase that interacts with the corepressor complex together with the highly active class I deacetylase HDAC3. The binding site of class IIa deacetylases was previously mapped to an approximate 500 amino acid region of SMRT, with recent implication of short glycine-serine-isoleucine (GSI) containing motifs. In order to characterize the interaction in detail, we applied a random library screening approach within this region and obtained a range of stable, soluble SMRT fragments. In agreement with an absence of predicted structural domains, these were characterized as intrinsically disordered by NMR spectroscopy. We identified one of them, comprising residues 1255-1452, as interacting with HDAC7 with micromolar affinity. The binding site was mapped in detail by NMR and confirmed by truncation and alanine mutagenesis. Complementing this with mutational analysis of HDAC7, we show that HDAC7, via its surface zinc ion binding site, binds to a 28 residue stretch in SMRT comprising a GSI motif followed by an alpha helix.
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Article dans une revue
Scientific Reports, Nature Publishing Group, 2017, 7 (1), pp.3678. 〈10.1038/s41598-017-03718-5〉
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http://hal.univ-grenoble-alpes.fr/hal-01561722
Contributeur : Frank Thomas <>
Soumis le : jeudi 13 juillet 2017 - 11:34:13
Dernière modification le : jeudi 11 janvier 2018 - 06:27:31

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Danielle C Desravines, Martin Serna Martin, Robert Schneider, Philippe J Mas, Nataliia Aleksandrova, et al.. Structural Characterization of the SMRT Corepressor Interacting with Histone Deacetylase 7.. Scientific Reports, Nature Publishing Group, 2017, 7 (1), pp.3678. 〈10.1038/s41598-017-03718-5〉. 〈hal-01561722〉

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