The histone chaperone Vps75 forms multiple oligomeric assemblies capable of mediating exchange between histone H3-H4 tetramers and Asf1-H3-H4 complexes.
The histone chaperone Vps75 forms multiple oligomeric assemblies capable of mediating exchange between histone H3-H4 tetramers and Asf1-H3-H4 complexes.
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DOI：
10.1093/nar/gkw209
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发表时间：
2016-07-27
影响因子：
14.9
通讯作者：
Owen-Hughes T
中科院分区：
文献类型：
--
作者：
Hammond CM;Sundaramoorthy R;Larance M;Lamond A;Stevens MA;El-Mkami H;Norman DG;Owen-Hughes T
Vps 75是一种组蛋白伴侣蛋白，其历史上被X射线晶体学表征为同源二聚体。在这项研究中，我们提出了一种晶体结构，其中包含两个相关的四聚体形式的Vps 75的晶格内。我们显示Vps 75与组蛋白在多个寡聚体。在等摩尔的H3-H4和Vps 75的存在下，主要的物质是与组蛋白H3-H4四聚体结合的重构的Vps 75四聚体。然而，在过量组蛋白的存在下，与组蛋白H3-H4四聚体结合的Vps 75二聚体占主导地位。我们发现Vps 75-H3-H4相互作用与组蛋白伴侣Asf 1是相容的，并利用脉冲电子-电子双共振（PELDOR）技术和交联MS/MS距离限制推导出Vps 75-Asf 1-H3-H4（VAH）共伴侣复合物的结构模型。该模型为Vps 75和Asf 1参与Rtt 109催化的组蛋白H3 K9乙酰化提供了分子基础。在Asf 1的情况下，该模型可用于产生由结合到H3-H4四聚体的重构Vps 75四聚体组成的复合物。这提供了一个结构的解释，为许多复杂的生化检测和说明的能力Vps 75相互作用的二聚体或四聚体H3-H4使用相同的相互作用表面。
Vps75 is a histone chaperone that has been historically characterized as homodimer by X-ray crystallography. In this study, we present a crystal structure containing two related tetrameric forms of Vps75 within the crystal lattice. We show Vps75 associates with histones in multiple oligomers. In the presence of equimolar H3–H4 and Vps75, the major species is a reconfigured Vps75 tetramer bound to a histone H3–H4 tetramer. However, in the presence of excess histones, a Vps75 dimer bound to a histone H3–H4 tetramer predominates. We show the Vps75–H3–H4 interaction is compatible with the histone chaperone Asf1 and deduce a structural model of the Vps75–Asf1-H3–H4 (VAH) co-chaperone complex using the Pulsed Electron-electron Double Resonance (PELDOR) technique and cross-linking MS/MS distance restraints. The model provides a molecular basis for the involvement of both Vps75 and Asf1 in Rtt109 catalysed histone H3 K9 acetylation. In the absence of Asf1 this model can be used to generate a complex consisting of a reconfigured Vps75 tetramer bound to a H3–H4 tetramer. This provides a structural explanation for many of the complexes detected biochemically and illustrates the ability of Vps75 to interact with dimeric or tetrameric H3–H4 using the same interaction surface.