Structural and Functional Analysis of the DEAF-1 and BS69 MYND Domains
文献类型：期刊论文
| 作者 | Kateb, Fatiha1,2,3; Perrin, Helene4; Tripsianes, Konstantinos1,2,3; Zou, Peijian1,2,3,5; Spadaccini, Roberta6; Bottomley, Matthew7; Franzmann, Titus M.2,3; Buchner, Johannes2,3; Ansieau, Stephane4; Sattler, Michael1,2,3,5 |
| 刊名 | PLOS ONE
 |
| 出版日期 | 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 |
| 源URL | [http://124.16.173.210/handle/834782/1251]  |
| 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). |
入库方式： OAI收割
来源：天津工业生物技术研究所
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