Cryo-EM structure of the SAGA and NuA4 coactivator subunit Tra1 at 3.7 angstrom resolution

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Abstract

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.

Data availability

The following data sets were generated

1. Cheung et al.
(2017) Coordinates of Tra1
5OJS.

https://www.rcsb.org/pdb/home/home.do
1. Cheung et al.
(2017) Electron Microscopy reconstructions
EMD-3824.

https://www.ebi.ac.uk/pdbe/emdb/

Article and author information

Author details

Luis Miguel Diaz-Santin

Department of Structural and Molecular Biology, University College London, Institute of Structural and Molecular Biology, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Natasha Lukoyanova

Biological Sciences, Birkbeck College, Institute of Structural and Molecular Biology, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Emir Aciyan

Biological Sciences, Birkbeck College, Institute of Structural and Molecular Biology, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Alan CM Cheung

Department of Structural and Molecular Biology, University College London, Institute of Structural and Molecular Biology, London, United Kingdom

For correspondence
alan.cheung@ucl.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6430-5127

Funding

Wellcome (102535/Z/13/Z)

Alan CM Cheung

Royal Society (RG140138)

Alan CM Cheung

University College London (Excellence Fellowship)

Alan CM Cheung

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.