Background:The Saccharomyces cerevisiae Spt-Ada-Gcn5 acetyltransferase (SAGA) complex regulates transcription through chromatin modification and other mechanisms. Results: The overall structure of SAGA and the arrangement of all subunits within this complex were determined. Conclusion: SAGA is flexible and is composed of core modules that support peripheral catalytic modules. Significance: Understanding the structural mechanisms of SAGA multifunctionality improves the understanding of other chromatin-modifying complexes.
Conserved from yeast to humans, the NuA4 histone acetyltransferase is a large multisubunit complex essential for cell viability through the regulation of gene expression, genome maintenance, metabolism, and cell fate during development and stress. How the different NuA4 subunits work in concert with one another to perform these diverse functions remains unclear, and addressing this central question requires a comprehensive understanding of NuA4's molecular architecture and subunit organization. We have determined the structure of fully assembled native yeast NuA4 by single-particle electron microscopy. Our data revealed that NuA4 adopts a trilobal overall architecture, with each of the three lobes constituted by one or two functional modules. By performing cross-linking coupled to mass spectrometry analysis and protein interaction studies, we further mapped novel intermolecular interfaces within NuA4. Finally, we combined these new data with other known structural information of NuA4 subunits and subassemblies to construct a multiscale model to illustrate how the different NuA4 subunits and modules are spatially arranged. This model shows that the multiple chromatin reader domains are clustered together around the catalytic core, suggesting that NuA4's multimodular architecture enables it to engage in multivalent interactions with its nucleosome substrate.
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