Cryo-EM structure of the SAGA and NuA4 coactivator subunit Tra1 at 3.7 angstrom resolution
Coactivator complexes SAGA and NuA4 stimulate transcription by post-translationally modifying chromatin. Both complexes contain the Tra1 subunit, a highly conserved 3744-residue protein from the Phosphoinositide 3-Kinase-related kinase (PIKK) family and a direct target for multiple sequence-specific...
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eLife Sciences Publications Ltd
2017-08-01
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Online Access: | https://elifesciences.org/articles/28384 |
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author | Luis Miguel Díaz-Santín Natasha Lukoyanova Emir Aciyan Alan CM Cheung |
author_facet | Luis Miguel Díaz-Santín Natasha Lukoyanova Emir Aciyan Alan CM Cheung |
author_sort | Luis Miguel Díaz-Santín |
collection | DOAJ |
description | Coactivator complexes SAGA and NuA4 stimulate transcription by post-translationally modifying chromatin. Both complexes contain the Tra1 subunit, a highly conserved 3744-residue protein from the Phosphoinositide 3-Kinase-related kinase (PIKK) family and a direct target for multiple sequence-specific activators. We present the Cryo-EM structure of Saccharomyces cerevsisae Tra1 to 3.7 Å resolution, revealing an extensive network of alpha-helical solenoids organized into a diamond ring conformation and is strikingly reminiscent of DNA-PKcs, suggesting a direct role for Tra1 in DNA repair. The structure was fitted into an existing SAGA EM reconstruction and reveals limited contact surfaces to Tra1, hence it does not act as a molecular scaffold within SAGA. Mutations that affect activator targeting are distributed across the Tra1 structure, but also cluster within the N-terminal Finger region, indicating the presence of an activator interaction site. The structure of Tra1 is a key milestone in deciphering the mechanism of multiple coactivator complexes. |
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language | English |
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spelling | doaj.art-db72d217be7c4d5f9f4457d0b7daf0d12022-12-22T03:52:31ZengeLife Sciences Publications LtdeLife2050-084X2017-08-01610.7554/eLife.28384Cryo-EM structure of the SAGA and NuA4 coactivator subunit Tra1 at 3.7 angstrom resolutionLuis Miguel Díaz-Santín0Natasha Lukoyanova1Emir Aciyan2Alan CM Cheung3https://orcid.org/0000-0001-6430-5127Department of Structural and Molecular Biology, Institute of Structural and Molecular Biology, University College London, London, United KingdomInstitute of Structural and Molecular Biology, Biological Sciences, Birkbeck College, London, United KingdomInstitute of Structural and Molecular Biology, Biological Sciences, Birkbeck College, London, United KingdomDepartment of Structural and Molecular Biology, Institute of Structural and Molecular Biology, University College London, London, United Kingdom; Institute of Structural and Molecular Biology, Biological Sciences, Birkbeck College, London, United KingdomCoactivator complexes SAGA and NuA4 stimulate transcription by post-translationally modifying chromatin. Both complexes contain the Tra1 subunit, a highly conserved 3744-residue protein from the Phosphoinositide 3-Kinase-related kinase (PIKK) family and a direct target for multiple sequence-specific activators. We present the Cryo-EM structure of Saccharomyces cerevsisae Tra1 to 3.7 Å resolution, revealing an extensive network of alpha-helical solenoids organized into a diamond ring conformation and is strikingly reminiscent of DNA-PKcs, suggesting a direct role for Tra1 in DNA repair. The structure was fitted into an existing SAGA EM reconstruction and reveals limited contact surfaces to Tra1, hence it does not act as a molecular scaffold within SAGA. Mutations that affect activator targeting are distributed across the Tra1 structure, but also cluster within the N-terminal Finger region, indicating the presence of an activator interaction site. The structure of Tra1 is a key milestone in deciphering the mechanism of multiple coactivator complexes.https://elifesciences.org/articles/28384chromatintranscription activationcoactivatorPIKKSAGANuA4 |
spellingShingle | Luis Miguel Díaz-Santín Natasha Lukoyanova Emir Aciyan Alan CM Cheung Cryo-EM structure of the SAGA and NuA4 coactivator subunit Tra1 at 3.7 angstrom resolution eLife chromatin transcription activation coactivator PIKK SAGA NuA4 |
title | Cryo-EM structure of the SAGA and NuA4 coactivator subunit Tra1 at 3.7 angstrom resolution |
title_full | Cryo-EM structure of the SAGA and NuA4 coactivator subunit Tra1 at 3.7 angstrom resolution |
title_fullStr | Cryo-EM structure of the SAGA and NuA4 coactivator subunit Tra1 at 3.7 angstrom resolution |
title_full_unstemmed | Cryo-EM structure of the SAGA and NuA4 coactivator subunit Tra1 at 3.7 angstrom resolution |
title_short | Cryo-EM structure of the SAGA and NuA4 coactivator subunit Tra1 at 3.7 angstrom resolution |
title_sort | cryo em structure of the saga and nua4 coactivator subunit tra1 at 3 7 angstrom resolution |
topic | chromatin transcription activation coactivator PIKK SAGA NuA4 |
url | https://elifesciences.org/articles/28384 |
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