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

Molecular and Cellular Biology
Dheva SetiaputraCalvin K Yip

Abstract

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 in vitro 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 cata...Continue Reading

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Citations

Nov 27, 2019·Biochemical Society Transactions·Alberto Elías-VillalobosDominique Helmlinger
Nov 22, 2019·Nature Communications·Alberto Elías-VillalobosDominique Helmlinger
Mar 11, 2020·Frontiers in Plant Science·Loreto Espinosa-CoresManuel Piñeiro
Sep 28, 2021·Molecular and Cellular Biology·Salar AhmadJacques Côté

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