Interactions between the Nse3 and Nse4 components of the SMC5-6 complex identify evolutionarily conserved interactions between MAGE and EID Families.
Interactions between the Nse3 and Nse4 components of the SMC5-6 complex identify evolutionarily conserved interactions between MAGE and EID Families.
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DOI：
10.1371/journal.pone.0017270
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发表时间：
2011-02-25
期刊：
影响因子：
3.7
通讯作者：
Palecek J
中科院分区：
文献类型：
--
作者：
Hudson JJ;Bednarova K;Kozakova L;Liao C;Guerineau M;Colnaghi R;Vidot S;Marek J;Bathula SR;Lehmann AR;Palecek J
SMC5-6蛋白复合物参与细胞对DNA损伤的反应。它由6-8个多肽组成，其中Nse1、Nse3和Nse4形成紧密的亚络合物。MAGEG1是Nse3的哺乳动物同源基因，是MAGE（黑色素瘤相关抗原）蛋白家族的创始成员，而Nse4与EID （e1a样分化抑制剂）转录抑制因子家族相关。利用定点诱变、蛋白-蛋白相互作用分析和分子模型，我们在Nse3的c端域上发现了一个与Nse4相互作用的保守疏水表面，并在其n端域上发现了与Nse1相互作用所必需的残基。我们发现这些相互作用在人类同源物中是保守的。此外，Nse3的哺乳动物同源物MAGEG1与Nse4的哺乳动物同源物之一NSE4b的相互作用导致核受体甾体生成因子1 （SF1）的转录共激活。在对Nse3-Nse4相互作用的进化保守性的研究中，我们发现几种MAGE蛋白可以与至少一种NSE4/EID蛋白相互作用。我们发现，尽管MAGE家族的进化多样化，但从酵母到人类的所有MAGE蛋白共有的特征疏水表面介导了其与NSE4/EID蛋白的结合。我们的工作为神秘的MAGE蛋白的相互作用、进化和功能提供了新的见解。
The SMC5-6 protein complex is involved in the cellular response to DNA damage. It is composed of 6–8 polypeptides, of which Nse1, Nse3 and Nse4 form a tight sub-complex. MAGEG1, the mammalian ortholog of Nse3, is the founding member of the MAGE (melanoma-associated antigen) protein family and Nse4 is related to the EID (E1A-like inhibitor of differentiation) family of transcriptional repressors. Using site-directed mutagenesis, protein-protein interaction analyses and molecular modelling, we have identified a conserved hydrophobic surface on the C-terminal domain of Nse3 that interacts with Nse4 and identified residues in its N-terminal domain that are essential for interaction with Nse1. We show that these interactions are conserved in the human orthologs. Furthermore, interaction of MAGEG1, the mammalian ortholog of Nse3, with NSE4b, one of the mammalian orthologs of Nse4, results in transcriptional co-activation of the nuclear receptor, steroidogenic factor 1 (SF1). In an examination of the evolutionary conservation of the Nse3-Nse4 interactions, we find that several MAGE proteins can interact with at least one of the NSE4/EID proteins. We have found that, despite the evolutionary diversification of the MAGE family, the characteristic hydrophobic surface shared by all MAGE proteins from yeast to humans mediates its binding to NSE4/EID proteins. Our work provides new insights into the interactions, evolution and functions of the enigmatic MAGE proteins.
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影响因子：
3.7
作者：
Caballero, Otavia L.;Zhao, Qi;Simpson, Andrew J.
通讯作者：
Simpson, Andrew J.
影响因子：
4.8
作者：
Askew, Emily B.;Bai, Suxia;Wilson, Elizabeth M.
通讯作者：
Wilson, Elizabeth M.
DOI：
10.1126/science.1164382
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Jones S;Zhang X;Lin JC;Leary RJ;Angenendt P;Mankoo P;Carter H;Siu IM;Gallia GL;Olivi A;McLendon R;Rasheed BA;Keir S;Nikolskaya T;Nikolsky Y;Busam DA;Tekleab H;Diaz LA Jr;Hartigan J;Smith DR;Strausberg RL;Marie SK;Shinjo SM;Yan H;Riggins GJ;Bigner DD;Karchin R;Papadopoulos N;Parmigiani G;Vogelstein B;Velculescu VE;Kinzler KW
通讯作者：
Kinzler KW
影响因子：
16
作者：
Doyle JM;Gao J;Wang J;Yang M;Potts PR
通讯作者：
Potts PR
影响因子：
11.4
作者：
Potts, Patrick Ryan;Porteus, Matthew H.;Yu, Hongtao
通讯作者：
Yu, Hongtao