Structural and Functional Analysis of the DEAF-1 and BS69 MYND Domains

	Structural and Functional Analysis of the DEAF-1 and BS69 MYND Domains
	Kateb, Fatiha 1,2,3; Perrin, Helene 4; Tripsianes, Konstantinos 1,2,3; Zou, Peijian 1,2,3,5; Spadaccini, Roberta 6; Bottomley, Matthew 7; Franzmann, Titus M.2,3; Buchner, Johannes 2,3; Ansieau, Stephane 4; Sattler, Michael 1,2,3,5
刊名	PLOS ONE
	2013-01-25
卷号	8 期号:1
英文摘要	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 beta beta alpha 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.
WOS标题词	Science & Technology
类目[WOS]	Multidisciplinary Sciences
研究领域[WOS]	Science & Technology - Other Topics
关键词[WOS]	MAGNETIC-RESONANCE RELAXATION ; NMR STRUCTURE CALCULATION ; AUTOMATED NOE ASSIGNMENT ; MODEL-FREE APPROACH ; PROTEIN STRUCTURES ; DNA-BINDING ; N-COR ; METHYLTRANSFERASE SMYD3 ; DIPOLAR COUPLINGS ; TRANSCRIPTION
收录类别	SCI
语种	英语
WOS记录号	WOS:000315210400025
内容类型	期刊论文
源URL	[http://124.16.173.210/handle/834782/1243]
专题	天津工业生物技术研究所_蛋白质工程实验室邹培建_期刊论文
作者单位	1.Helmholtz Zentrum Munchen, Inst Biol Struct, Neuherberg, Germany 2.Tech Univ Munich, Biomol NMR, Garching, Germany 3.Tech Univ Munich, Dept Chem, Ctr Integrated Prot Sci Munich, Garching, Germany 4.Univ Lyon 1, Ctr Leon Berard, Inst Natl Sante & Rech Med U590, F-69365 Lyon, France 5.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Tianjin, Peoples R China 6.Univ Naples Federico II, Dipartimento Chim, Naples, Italy 7.Novartis Vaccines & Diagnost, Siena, Italy
推荐引用方式 GB/T 7714	Kateb, Fatiha,Perrin, Helene,Tripsianes, Konstantinos,et al. Structural and Functional Analysis of the DEAF-1 and BS69 MYND Domains[J]. PLOS ONE,2013,8(1).
APA	Kateb, Fatiha.,Perrin, Helene.,Tripsianes, Konstantinos.,Zou, Peijian.,Spadaccini, Roberta.,...&Sattler, Michael.(2013).Structural and Functional Analysis of the DEAF-1 and BS69 MYND Domains.PLOS ONE,8(1).
MLA	Kateb, Fatiha,et al."Structural and Functional Analysis of the DEAF-1 and BS69 MYND Domains".PLOS ONE 8.1(2013).