Linking functions: an additional role for an intrinsically disordered linker domain in the transcriptional coactivator CBP

Abstract The multi-domain transcriptional coactivators CBP/p300 integrate a multitude of signaling inputs, interacting with more than 400 proteins via one or more of their globular domains. While CBP/p300 function is typically considered in terms of these structured domains, about half of the protei...

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Autores principales:	Sara Contreras-Martos, Alessandro Piai, Simone Kosol, Mihaly Varadi, Angela Bekesi, Pierre Lebrun, Alexander N. Volkov, Kris Gevaert, Roberta Pierattelli, Isabella C. Felli, Peter Tompa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8a627968a1b743338820c4514ae21356
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spelling	oai:doaj.org-article:8a627968a1b743338820c4514ae213562021-12-02T11:40:21ZLinking functions: an additional role for an intrinsically disordered linker domain in the transcriptional coactivator CBP10.1038/s41598-017-04611-x2045-2322https://doaj.org/article/8a627968a1b743338820c4514ae213562017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04611-xhttps://doaj.org/toc/2045-2322Abstract The multi-domain transcriptional coactivators CBP/p300 integrate a multitude of signaling inputs, interacting with more than 400 proteins via one or more of their globular domains. While CBP/p300 function is typically considered in terms of these structured domains, about half of the protein consists of intrinsically disordered regions (IDRs) of varying length. However, these IDRs have only been thought of as linkers that allow flexible spatial arrangement of the structured domains, but recent studies have shown that similar IDRs mediate specific and critical interactions in other proteins. To examine the roles of IDRs in CBP, we performed yeast-two-hybrid screenings of placenta and lung cancer cDNA libraries, which demonstrated that the long IDR linking the KIX domain and bromodomain of CBP (termed ID3) can potentially bind to several proteins. The RNA-binding Zinc-finger protein 106 (ZFP106) detected in both libraries was identified as a novel substrate for CBP-mediated acetylation. Nuclear magnetic resonance (NMR) spectroscopy combined with cross-linking experiments and competition-binding assays showed that the fully disordered isolated ID3 transiently interacts with an IDR of ZFP106 in a fashion that disorder of both regions is maintained. These findings demonstrate that beside the linking function, ID3 can also interact with acetylation substrates of CBP.Sara Contreras-MartosAlessandro PiaiSimone KosolMihaly VaradiAngela BekesiPierre LebrunAlexander N. VolkovKris GevaertRoberta PierattelliIsabella C. FelliPeter TompaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sara Contreras-Martos Alessandro Piai Simone Kosol Mihaly Varadi Angela Bekesi Pierre Lebrun Alexander N. Volkov Kris Gevaert Roberta Pierattelli Isabella C. Felli Peter Tompa Linking functions: an additional role for an intrinsically disordered linker domain in the transcriptional coactivator CBP
description	Abstract The multi-domain transcriptional coactivators CBP/p300 integrate a multitude of signaling inputs, interacting with more than 400 proteins via one or more of their globular domains. While CBP/p300 function is typically considered in terms of these structured domains, about half of the protein consists of intrinsically disordered regions (IDRs) of varying length. However, these IDRs have only been thought of as linkers that allow flexible spatial arrangement of the structured domains, but recent studies have shown that similar IDRs mediate specific and critical interactions in other proteins. To examine the roles of IDRs in CBP, we performed yeast-two-hybrid screenings of placenta and lung cancer cDNA libraries, which demonstrated that the long IDR linking the KIX domain and bromodomain of CBP (termed ID3) can potentially bind to several proteins. The RNA-binding Zinc-finger protein 106 (ZFP106) detected in both libraries was identified as a novel substrate for CBP-mediated acetylation. Nuclear magnetic resonance (NMR) spectroscopy combined with cross-linking experiments and competition-binding assays showed that the fully disordered isolated ID3 transiently interacts with an IDR of ZFP106 in a fashion that disorder of both regions is maintained. These findings demonstrate that beside the linking function, ID3 can also interact with acetylation substrates of CBP.
format	article
author	Sara Contreras-Martos Alessandro Piai Simone Kosol Mihaly Varadi Angela Bekesi Pierre Lebrun Alexander N. Volkov Kris Gevaert Roberta Pierattelli Isabella C. Felli Peter Tompa
author_facet	Sara Contreras-Martos Alessandro Piai Simone Kosol Mihaly Varadi Angela Bekesi Pierre Lebrun Alexander N. Volkov Kris Gevaert Roberta Pierattelli Isabella C. Felli Peter Tompa
author_sort	Sara Contreras-Martos
title	Linking functions: an additional role for an intrinsically disordered linker domain in the transcriptional coactivator CBP
title_short	Linking functions: an additional role for an intrinsically disordered linker domain in the transcriptional coactivator CBP
title_full	Linking functions: an additional role for an intrinsically disordered linker domain in the transcriptional coactivator CBP
title_fullStr	Linking functions: an additional role for an intrinsically disordered linker domain in the transcriptional coactivator CBP
title_full_unstemmed	Linking functions: an additional role for an intrinsically disordered linker domain in the transcriptional coactivator CBP
title_sort	linking functions: an additional role for an intrinsically disordered linker domain in the transcriptional coactivator cbp
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8a627968a1b743338820c4514ae21356
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Linking functions: an additional role for an intrinsically disordered linker domain in the transcriptional coactivator CBP

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