Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6

Abstract Crucial for immune and anti-inflammatory cellular responses, signal transducer and activator of transcription 6 (STAT6) regulates transcriptional activation in response to interleukin-4 and -13 -induced tyrosine phosphorylation by direct interaction with coactivators. The interaction of STA...

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Autores principales:	Luigi Russo, Karin Giller, Edith Pfitzner, Christian Griesinger, Stefan Becker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5c5e90f76ccf4f7e85674087861c4afe
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spelling	oai:doaj.org-article:5c5e90f76ccf4f7e85674087861c4afe2021-12-02T15:05:15ZInsight into the molecular recognition mechanism of the coactivator NCoA1 by STAT610.1038/s41598-017-17088-52045-2322https://doaj.org/article/5c5e90f76ccf4f7e85674087861c4afe2017-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-17088-5https://doaj.org/toc/2045-2322Abstract Crucial for immune and anti-inflammatory cellular responses, signal transducer and activator of transcription 6 (STAT6) regulates transcriptional activation in response to interleukin-4 and -13 -induced tyrosine phosphorylation by direct interaction with coactivators. The interaction of STAT6 with nuclear coactivator 1 (NCoA1) is mediated by a short region of the STAT6 transactivation domain that includes the motif LXXLL and interacts with the PAS-B domain of NCoA1. Despite the availability of an X-ray structure of the PAS-B domain/ Leu794-Gly814-STAT6 complex, the mechanistic details of this interaction are still poorly understood. Here, we determine the structure of the NCoA1257–385/STAT6783–814 complex using Nuclear Magnetic Resonance (NMR) and X-ray crystallography. The STAT6783–814 peptide binds with additional N-terminal amino acids to NCoA1257–385, compared to the STAT6794–814 peptide, explaining its higher affinity. Secondary and tertiary structures existing in the free peptide are more highly populated in the complex, suggesting binding by conformational selection.Luigi RussoKarin GillerEdith PfitznerChristian GriesingerStefan BeckerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luigi Russo Karin Giller Edith Pfitzner Christian Griesinger Stefan Becker Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6
description	Abstract Crucial for immune and anti-inflammatory cellular responses, signal transducer and activator of transcription 6 (STAT6) regulates transcriptional activation in response to interleukin-4 and -13 -induced tyrosine phosphorylation by direct interaction with coactivators. The interaction of STAT6 with nuclear coactivator 1 (NCoA1) is mediated by a short region of the STAT6 transactivation domain that includes the motif LXXLL and interacts with the PAS-B domain of NCoA1. Despite the availability of an X-ray structure of the PAS-B domain/ Leu794-Gly814-STAT6 complex, the mechanistic details of this interaction are still poorly understood. Here, we determine the structure of the NCoA1257–385/STAT6783–814 complex using Nuclear Magnetic Resonance (NMR) and X-ray crystallography. The STAT6783–814 peptide binds with additional N-terminal amino acids to NCoA1257–385, compared to the STAT6794–814 peptide, explaining its higher affinity. Secondary and tertiary structures existing in the free peptide are more highly populated in the complex, suggesting binding by conformational selection.
format	article
author	Luigi Russo Karin Giller Edith Pfitzner Christian Griesinger Stefan Becker
author_facet	Luigi Russo Karin Giller Edith Pfitzner Christian Griesinger Stefan Becker
author_sort	Luigi Russo
title	Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6
title_short	Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6
title_full	Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6
title_fullStr	Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6
title_full_unstemmed	Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6
title_sort	insight into the molecular recognition mechanism of the coactivator ncoa1 by stat6
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5c5e90f76ccf4f7e85674087861c4afe
work_keys_str_mv	AT luigirusso insightintothemolecularrecognitionmechanismofthecoactivatorncoa1bystat6 AT karingiller insightintothemolecularrecognitionmechanismofthecoactivatorncoa1bystat6 AT edithpfitzner insightintothemolecularrecognitionmechanismofthecoactivatorncoa1bystat6 AT christiangriesinger insightintothemolecularrecognitionmechanismofthecoactivatorncoa1bystat6 AT stefanbecker insightintothemolecularrecognitionmechanismofthecoactivatorncoa1bystat6
_version_	1718388891182956544

Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6

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