Structural and functional analysis of the DEAF-1 and BS69 MYND domains.

DEAF-1 is an important transcriptional regulator that is required for embryonic development and is linked to clinical depression and suicidal behavior in humans. It comprises various structural domains, including a SAND domain that mediates DNA binding and a MYND domain, a cysteine-rich module organ...

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Autores principales:	Fatiha Kateb, Helene Perrin, Konstantinos Tripsianes, Peijian Zou, Roberta Spadaccini, Matthew Bottomley, Titus M Franzmann, Johannes Buchner, Stephane Ansieau, Michael Sattler
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a1571d910172426ca543df14c3437e45
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spelling	oai:doaj.org-article:a1571d910172426ca543df14c3437e452021-11-18T07:59:52ZStructural and functional analysis of the DEAF-1 and BS69 MYND domains.1932-620310.1371/journal.pone.0054715https://doaj.org/article/a1571d910172426ca543df14c3437e452013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23372760/?tool=EBIhttps://doaj.org/toc/1932-6203DEAF-1 is an important transcriptional regulator that is required for embryonic development and is linked to clinical depression and suicidal behavior in humans. It comprises various structural domains, including a SAND domain that mediates DNA binding and a MYND domain, a cysteine-rich module organized in a Cys(4)-Cys(2)-His-Cys (C4-C2HC) tandem zinc binding motif. DEAF-1 transcription regulation activity is mediated through interactions with cofactors such as NCoR and SMRT. Despite the important biological role of the DEAF-1 protein, little is known regarding the structure and binding properties of its MYND domain.Here, we report the solution structure, dynamics and ligand binding of the human DEAF-1 MYND domain encompassing residues 501-544 determined by NMR spectroscopy. The structure adopts a ββα fold that exhibits tandem zinc-binding sites with a cross-brace topology, similar to the MYND domains in AML1/ETO and other proteins. We show that the DEAF-1 MYND domain binds to peptides derived from SMRT and NCoR corepressors. The binding surface mapped by NMR titrations is similar to the one previously reported for AML1/ETO. The ligand binding and molecular functions of the related BS69 MYND domain were studied based on a homology model and mutational analysis. Interestingly, the interaction between BS69 and its binding partners (viral and cellular proteins) seems to require distinct charged residues flanking the predicted MYND domain fold, suggesting a different binding mode. Our findings demonstrate that the MYND domain is a conserved zinc binding fold that plays important roles in transcriptional regulation by mediating distinct molecular interactions with viral and cellular proteins.Fatiha KatebHelene PerrinKonstantinos TripsianesPeijian ZouRoberta SpadacciniMatthew BottomleyTitus M FranzmannJohannes BuchnerStephane AnsieauMichael SattlerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e54715 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fatiha Kateb Helene Perrin Konstantinos Tripsianes Peijian Zou Roberta Spadaccini Matthew Bottomley Titus M Franzmann Johannes Buchner Stephane Ansieau Michael Sattler Structural and functional analysis of the DEAF-1 and BS69 MYND domains.
description	DEAF-1 is an important transcriptional regulator that is required for embryonic development and is linked to clinical depression and suicidal behavior in humans. It comprises various structural domains, including a SAND domain that mediates DNA binding and a MYND domain, a cysteine-rich module organized in a Cys(4)-Cys(2)-His-Cys (C4-C2HC) tandem zinc binding motif. DEAF-1 transcription regulation activity is mediated through interactions with cofactors such as NCoR and SMRT. Despite the important biological role of the DEAF-1 protein, little is known regarding the structure and binding properties of its MYND domain.Here, we report the solution structure, dynamics and ligand binding of the human DEAF-1 MYND domain encompassing residues 501-544 determined by NMR spectroscopy. The structure adopts a ββα fold that exhibits tandem zinc-binding sites with a cross-brace topology, similar to the MYND domains in AML1/ETO and other proteins. We show that the DEAF-1 MYND domain binds to peptides derived from SMRT and NCoR corepressors. The binding surface mapped by NMR titrations is similar to the one previously reported for AML1/ETO. The ligand binding and molecular functions of the related BS69 MYND domain were studied based on a homology model and mutational analysis. Interestingly, the interaction between BS69 and its binding partners (viral and cellular proteins) seems to require distinct charged residues flanking the predicted MYND domain fold, suggesting a different binding mode. Our findings demonstrate that the MYND domain is a conserved zinc binding fold that plays important roles in transcriptional regulation by mediating distinct molecular interactions with viral and cellular proteins.
format	article
author	Fatiha Kateb Helene Perrin Konstantinos Tripsianes Peijian Zou Roberta Spadaccini Matthew Bottomley Titus M Franzmann Johannes Buchner Stephane Ansieau Michael Sattler
author_facet	Fatiha Kateb Helene Perrin Konstantinos Tripsianes Peijian Zou Roberta Spadaccini Matthew Bottomley Titus M Franzmann Johannes Buchner Stephane Ansieau Michael Sattler
author_sort	Fatiha Kateb
title	Structural and functional analysis of the DEAF-1 and BS69 MYND domains.
title_short	Structural and functional analysis of the DEAF-1 and BS69 MYND domains.
title_full	Structural and functional analysis of the DEAF-1 and BS69 MYND domains.
title_fullStr	Structural and functional analysis of the DEAF-1 and BS69 MYND domains.
title_full_unstemmed	Structural and functional analysis of the DEAF-1 and BS69 MYND domains.
title_sort	structural and functional analysis of the deaf-1 and bs69 mynd domains.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a1571d910172426ca543df14c3437e45
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_version_	1718422685334110208

Structural and functional analysis of the DEAF-1 and BS69 MYND domains.

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