Molecular Architecture of the Essential Yeast Histone Acetyltransferase Complex NuA4 Redefines Its Multimodularity

• DOI: 10.1128/mcb.00570-17
• Publication Date: 2018-02-15T10:09:20Z
• Authors: Dheva Setiaputra; Salar Ahmad; Udit Dalwadi; Anne-Lise Steunou; Shan Lu; James D. Ross; Meng-Qiu Dong; Jacques Côté; Calvin K. Yip
• Keywords: Histone acetyltransferase; Acetyltransferases

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