Interactions between the Nse3 and Nse4 components of the SMC5-6 complex identify evolutionarily conserved interactions between MAGE and EID Families.

<h4>Background</h4>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 ant...

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Main Authors: Jessica J R Hudson, Katerina Bednarova, Lucie Kozakova, Chunyan Liao, Marc Guerineau, Rita Colnaghi, Susanne Vidot, Jaromir Marek, Sreenivas R Bathula, Alan R Lehmann, Jan Palecek
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-02-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0017270&type=printable
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author Jessica J R Hudson
Katerina Bednarova
Lucie Kozakova
Chunyan Liao
Marc Guerineau
Rita Colnaghi
Susanne Vidot
Jaromir Marek
Sreenivas R Bathula
Alan R Lehmann
Jan Palecek
author_facet Jessica J R Hudson
Katerina Bednarova
Lucie Kozakova
Chunyan Liao
Marc Guerineau
Rita Colnaghi
Susanne Vidot
Jaromir Marek
Sreenivas R Bathula
Alan R Lehmann
Jan Palecek
author_sort Jessica J R Hudson
collection DOAJ
description <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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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spelling doaj-art-4f1de5e8a09e4934a044c2ab47f7b49f2025-08-20T02:08:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-02-0162e1727010.1371/journal.pone.0017270Interactions between the Nse3 and Nse4 components of the SMC5-6 complex identify evolutionarily conserved interactions between MAGE and EID Families.Jessica J R HudsonKaterina BednarovaLucie KozakovaChunyan LiaoMarc GuerineauRita ColnaghiSusanne VidotJaromir MarekSreenivas R BathulaAlan R LehmannJan Palecek<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0017270&type=printable
spellingShingle Jessica J R Hudson
Katerina Bednarova
Lucie Kozakova
Chunyan Liao
Marc Guerineau
Rita Colnaghi
Susanne Vidot
Jaromir Marek
Sreenivas R Bathula
Alan R Lehmann
Jan Palecek
Interactions between the Nse3 and Nse4 components of the SMC5-6 complex identify evolutionarily conserved interactions between MAGE and EID Families.
PLoS ONE
title Interactions between the Nse3 and Nse4 components of the SMC5-6 complex identify evolutionarily conserved interactions between MAGE and EID Families.
title_full Interactions between the Nse3 and Nse4 components of the SMC5-6 complex identify evolutionarily conserved interactions between MAGE and EID Families.
title_fullStr Interactions between the Nse3 and Nse4 components of the SMC5-6 complex identify evolutionarily conserved interactions between MAGE and EID Families.
title_full_unstemmed Interactions between the Nse3 and Nse4 components of the SMC5-6 complex identify evolutionarily conserved interactions between MAGE and EID Families.
title_short Interactions between the Nse3 and Nse4 components of the SMC5-6 complex identify evolutionarily conserved interactions between MAGE and EID Families.
title_sort interactions between the nse3 and nse4 components of the smc5 6 complex identify evolutionarily conserved interactions between mage and eid families
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0017270&type=printable
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