Unveiling the dimer/monomer propensities of Smad MH1-DNA complexes
Smad transcription factors are the main downstream effectors of the Transforming growth factor β superfamily (TGFβ) signalling network. The DNA complexes determined here by X-ray crystallography for the Bone Morphogenetic Proteins (BMP) activated Smad5 and Smad8 proteins reveal that all MH1 domains...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037021000027 |
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| author | Lidia Ruiz Zuzanna Kaczmarska Tiago Gomes Eric Aragon Carles Torner Regina Freier Blazej Baginski Pau Martin-Malpartida Natàlia de Martin Garrido José. A. Marquez Tiago N. Cordeiro Radoslaw Pluta Maria J. Macias |
| author_facet | Lidia Ruiz Zuzanna Kaczmarska Tiago Gomes Eric Aragon Carles Torner Regina Freier Blazej Baginski Pau Martin-Malpartida Natàlia de Martin Garrido José. A. Marquez Tiago N. Cordeiro Radoslaw Pluta Maria J. Macias |
| author_sort | Lidia Ruiz |
| collection | DOAJ |
| description | Smad transcription factors are the main downstream effectors of the Transforming growth factor β superfamily (TGFβ) signalling network. The DNA complexes determined here by X-ray crystallography for the Bone Morphogenetic Proteins (BMP) activated Smad5 and Smad8 proteins reveal that all MH1 domains bind [GGC(GC)|(CG)] motifs similarly, although TGFβ-activated Smad2/3 and Smad4 MH1 domains bind as monomers whereas Smad1/5/8 form helix-swapped dimers. Dimers and monomers are also present in solution, as revealed by NMR. To decipher the characteristics that defined these dimers, we designed chimeric MH1 domains and characterized them using X-ray crystallography. We found that swapping the loop1 between TGFβ- and BMP- activated MH1 domains switches the dimer/monomer propensities. When we scanned the distribution of Smad-bound motifs in ChIP-Seq peaks (Chromatin immunoprecipitation followed by high-throughput sequencing) in Smad-responsive genes, we observed specific site clustering and spacing depending on whether the peaks correspond to BMP- or TGFβ-responsive genes. We also identified significant correlations between site distribution and monomer or dimer propensities. We propose that the MH1 monomer or dimer propensity of Smads contributes to the distinct motif selection genome-wide and together with the MH2 domain association, help define the composition of R-Smad/Smad4 trimeric complexes. |
| first_indexed | 2024-12-20T17:01:54Z |
| format | Article |
| id | doaj.art-10ae5e5507dd41e3bcbef079abb5af1f |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-12-20T17:01:54Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-10ae5e5507dd41e3bcbef079abb5af1f2022-12-21T19:32:30ZengElsevierComputational and Structural Biotechnology Journal2001-03702021-01-0119632646Unveiling the dimer/monomer propensities of Smad MH1-DNA complexesLidia Ruiz0Zuzanna Kaczmarska1Tiago Gomes2Eric Aragon3Carles Torner4Regina Freier5Blazej Baginski6Pau Martin-Malpartida7Natàlia de Martin Garrido8José. A. Marquez9Tiago N. Cordeiro10Radoslaw Pluta11Maria J. Macias12Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, Barcelona 08028, SpainEMBL Grenoble, 71 Avenue des Martyrs, CS 90181, Grenoble Cedex 9 38042, France; International Institute of Molecular and Cell Biology in Warsaw, Trojdena 4, Warsaw 02-109, PolandInstitute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, Barcelona 08028, SpainInstitute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, Barcelona 08028, SpainInstitute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, Barcelona 08028, SpainInstitute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, Barcelona 08028, SpainInstitute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, Barcelona 08028, SpainInstitute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, Barcelona 08028, SpainInstitute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, Barcelona 08028, SpainEMBL Grenoble, 71 Avenue des Martyrs, CS 90181, Grenoble Cedex 9 38042, FranceInstituto de Tecnologia Química e Biológica António Xavier (ITQB), Universidade NOVA de Lisboa, Av. da República, 2780-157 Oeiras, PortugalInstitute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, Barcelona 08028, Spain; Corresponding authors at: Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, Barcelona 08028, Spain.Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, Barcelona 08028, Spain; ICREA, Passeig Lluís Companys 23, Barcelona 08010, Spain; Corresponding authors at: Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, Barcelona 08028, Spain.Smad transcription factors are the main downstream effectors of the Transforming growth factor β superfamily (TGFβ) signalling network. The DNA complexes determined here by X-ray crystallography for the Bone Morphogenetic Proteins (BMP) activated Smad5 and Smad8 proteins reveal that all MH1 domains bind [GGC(GC)|(CG)] motifs similarly, although TGFβ-activated Smad2/3 and Smad4 MH1 domains bind as monomers whereas Smad1/5/8 form helix-swapped dimers. Dimers and monomers are also present in solution, as revealed by NMR. To decipher the characteristics that defined these dimers, we designed chimeric MH1 domains and characterized them using X-ray crystallography. We found that swapping the loop1 between TGFβ- and BMP- activated MH1 domains switches the dimer/monomer propensities. When we scanned the distribution of Smad-bound motifs in ChIP-Seq peaks (Chromatin immunoprecipitation followed by high-throughput sequencing) in Smad-responsive genes, we observed specific site clustering and spacing depending on whether the peaks correspond to BMP- or TGFβ-responsive genes. We also identified significant correlations between site distribution and monomer or dimer propensities. We propose that the MH1 monomer or dimer propensity of Smads contributes to the distinct motif selection genome-wide and together with the MH2 domain association, help define the composition of R-Smad/Smad4 trimeric complexes.http://www.sciencedirect.com/science/article/pii/S2001037021000027SmadTranscription factorProtein-DNAMH1 domainBMP signalingSmad5 |
| spellingShingle | Lidia Ruiz Zuzanna Kaczmarska Tiago Gomes Eric Aragon Carles Torner Regina Freier Blazej Baginski Pau Martin-Malpartida Natàlia de Martin Garrido José. A. Marquez Tiago N. Cordeiro Radoslaw Pluta Maria J. Macias Unveiling the dimer/monomer propensities of Smad MH1-DNA complexes Computational and Structural Biotechnology Journal Smad Transcription factor Protein-DNA MH1 domain BMP signaling Smad5 |
| title | Unveiling the dimer/monomer propensities of Smad MH1-DNA complexes |
| title_full | Unveiling the dimer/monomer propensities of Smad MH1-DNA complexes |
| title_fullStr | Unveiling the dimer/monomer propensities of Smad MH1-DNA complexes |
| title_full_unstemmed | Unveiling the dimer/monomer propensities of Smad MH1-DNA complexes |
| title_short | Unveiling the dimer/monomer propensities of Smad MH1-DNA complexes |
| title_sort | unveiling the dimer monomer propensities of smad mh1 dna complexes |
| topic | Smad Transcription factor Protein-DNA MH1 domain BMP signaling Smad5 |
| url | http://www.sciencedirect.com/science/article/pii/S2001037021000027 |
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