Stabilization of the hexasome intermediate during histone exchange by yeast SWR1 complex

IF 14.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Adam S.B. Jalal, Paul Girvan, Eugene Y.D. Chua, Lexin Liu, Shijie Wang, Elizabeth A. McCormack, Michael T. Skehan, Carol L. Knight, David S. Rueda, Dale B. Wigley
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引用次数: 0

Abstract

The yeast SWR1 complex catalyzes the exchange of histone H2A/H2B dimers in nucleosomes with Htz1/H2B dimers. We use cryoelectron microscopy to determine the structure of an enzyme-bound hexasome intermediate in the reaction pathway of histone exchange, in which an H2A/H2B dimer has been extracted from a nucleosome prior to the insertion of a dimer comprising Htz1/H2B. The structure reveals a key role for the Swc5 subunit in stabilizing the unwrapping of DNA from the histone core of the hexasome. By engineering a crosslink between an Htz1/H2B dimer and its chaperone protein Chz1, we show that this blocks histone exchange by SWR1 but allows the incoming chaperone-dimer complex to insert into the hexasome. We use this reagent to trap an SWR1/hexasome complex with an incoming Htz1/H2B dimer that shows how the reaction progresses to the next step. Taken together the structures reveal insights into the mechanism of histone exchange by SWR1 complex.

Abstract Image

酵母 SWR1 复合物在组蛋白交换过程中稳定六聚体中间体
酵母 SWR1 复合物催化核小体中组蛋白 H2A/H2B 二聚体与 Htz1/H2B 二聚体的交换。我们利用冷冻电子显微镜确定了组蛋白交换反应途径中酶结合六聚体中间体的结构,在该中间体中,H2A/H2B二聚体在插入由Htz1/H2B组成的二聚体之前已从核小体中提取出来。该结构揭示了 Swc5 亚基在稳定 DNA 从六聚体的组蛋白核心解开方面的关键作用。通过在 Htz1/H2B 二聚体和它的伴侣蛋白 Chz1 之间建立交联,我们发现这阻止了 SWR1 的组蛋白交换,但允许进入的伴侣蛋白二聚体复合物插入六聚体。我们用这种试剂捕获了一个带有进入的 Htz1/H2B 二聚体的 SWR1/六聚体复合物,展示了反应如何进行到下一步。总之,这些结构揭示了 SWR1 复合物交换组蛋白的机制。
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来源期刊
Molecular Cell
Molecular Cell 生物-生化与分子生物学
CiteScore
26.00
自引率
3.80%
发文量
389
审稿时长
1 months
期刊介绍: Molecular Cell is a companion to Cell, the leading journal of biology and the highest-impact journal in the world. Launched in December 1997 and published monthly. Molecular Cell is dedicated to publishing cutting-edge research in molecular biology, focusing on fundamental cellular processes. The journal encompasses a wide range of topics, including DNA replication, recombination, and repair; Chromatin biology and genome organization; Transcription; RNA processing and decay; Non-coding RNA function; Translation; Protein folding, modification, and quality control; Signal transduction pathways; Cell cycle and checkpoints; Cell death; Autophagy; Metabolism.
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