酿酒酵母 NuA4/TIP60 复合物的结构。

Architecture of the Saccharomyces cerevisiae NuA4/TIP60 complex.

机构信息

Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, 230026, China.

CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Hefei, 230026, China.

出版信息

Nat Commun. 2018 Mar 20;9(1):1147. doi: 10.1038/s41467-018-03504-5.

DOI:10.1038/s41467-018-03504-5

PMID:29559617

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5861120/

Abstract

The NuA4/TIP60 acetyltransferase complex is required for gene regulation, DNA repair and cell cycle progression. The limited structural information impeded understanding of NuA4/TIP60 assembly and regulatory mechanism. Here, we report the 4.7 Å cryo-electron microscopy (cryo-EM) structure of a NuA4/TIP60 TEEAA assembly (Tra1, Eaf1, Eaf5, actin and Arp4) and the 7.6 Å cryo-EM structure of a TEEAA-piccolo assembly (Esa1, Epl1, Yng2 and Eaf6). The Tra1 and Eaf1 constitute the assembly scaffold. The Eaf1 SANT domain tightly binds to the LBE and FATC domains of Tra1 by ionic interactions. The actin/Arp4 peripherally associates with Eaf1 HSA domain. The Eaf5/7/3 (TINTIN) and piccolo modules largely pack against the FAT and HEAT repeats of Tra1 and their association depends on Eaf1 N-terminal and HSA regions, respectively. These structures elucidate the detailed architecture and molecular interactions between NuA4 subunits and offer exciting insights into the scaffolding and regulatory mechanisms of Tra1 pseudokinase.

摘要

NuA4/TIP60 乙酰转移酶复合物对于基因调控、DNA 修复和细胞周期进程是必需的。有限的结构信息阻碍了对 NuA4/TIP60 组装和调节机制的理解。在这里，我们报告了 NuA4/TIP60 TEEAA 组装（Tra1、Eaf1、Eaf5、肌动蛋白和 Arp4）的 4.7Å 冷冻电镜（cryo-EM）结构和 TEEAA-piccolo 组装（Esa1、Epl1、Yng2 和 Eaf6）的 7.6Å cryo-EM 结构。Tra1 和 Eaf1 构成了组装支架。Eaf1 的 SANT 结构域通过离子相互作用与 Tra1 的 LBE 和 FATC 结构域紧密结合。肌动蛋白/Arp4 与 Eaf1 HSA 结构域的外周相关。Eaf5/7/3（TINTIN）和 piccolo 模块主要与 Tra1 的 FAT 和 HEAT 重复序列结合，它们的结合分别取决于 Eaf1 的 N 端和 HSA 区域。这些结构阐明了 NuA4 亚基之间的详细结构和分子相互作用，并为 Tra1 拟激酶的支架和调节机制提供了令人兴奋的见解。