Crystal structures of fission yeast histone chaperone Asf1 complexed with the Hip1 B-domain or the Cac2 C terminus
Crystal structures of fission yeast histone chaperone Asf1 complexed with the Hip1 B-domain or the Cac2 C terminus
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DOI：
10.1074/jbc.m800594200
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发表时间：
2008-05-16
影响因子：
4.8
通讯作者：
Yokoyama, Shigeyuki
中科院分区：
文献类型：
--
作者：
Malay, Ali D.;Umehara, Takashi;Yokoyama, Shigeyuki
核心组蛋白在真核DNA上的组装是由几个组蛋白伴侣复合物调节的，包括Asf1、ca -1和HIRA。Asf1是一种独特的组蛋白伴侣蛋白，既参与复制依赖途径，也参与复制独立途径。在这里，我们报道了裂变酵母Asf1/Cia1 （SpAsf1N；残基1-161）的载子形式的晶体结构，以及它与裂变酵母HIRA同源物Hip1 （Hip1B）的b结构域和CAF-1的Cac2亚基（Cac2C）的c端区域的配合物。分裂酵母对Asf1N-Hip1B的识别模式与人类对Asf1-HIRA的识别模式相似，表明Asf1N对Hip1B/HIRA的识别从酵母到哺乳动物都是保守的。有趣的是，Hip1B和Cac2C与Asf1表现出非常相似的相互作用模式。Asf1N的D37A和L60A/V62A突变几乎完全消除了Asf1N与Hip1B之间的结合，表明盐桥和范德华接触在复合物形成中的关键作用。与此一致的是，上述两种Asf1突变也显著降低了与Cac2C的结合。这些结果为ca -1和HIRA/Hip1相互排斥的Asf1结合模型提供了结构基础，其中Asf1和ca -1在复制依赖途径中组装组蛋白H3/H4（在脊椎动物中为H3.1/H4），而Asf1和HIRA/Hip1在复制独立途径中组装组蛋白H3/H4（在脊椎动物中为H3.3/H4）。
The assembly of core histones onto eukaryotic DNA is modulated by several histone chaperone complexes, including Asf1, CAF-1, and HIRA. Asf1 is a unique histone chaperone that participates in both the replication-dependent and replication-independent pathways. Here we report the crystal structures of the apo-form of fission yeast Asf1/Cia1 (SpAsf1N; residues 1-161) as well as its complexes with the B-domain of the fission yeast HIRA orthologue Hip1 (Hip1B) and the C-terminal region of the Cac2 subunit of CAF-1 (Cac2C). The mode of the fission yeast Asf1N-Hip1B recognition is similar to that of the human Asf1-HIRA recognition, suggesting that Asf1N recognition of Hip1B/HIRA is conserved from yeast to mammals. Interestingly, Hip1B and Cac2C show remarkably similar interaction modes with Asf1. The binding between Asf1N and Hip1B was almost completely abolished by the D37A and L60A/V62A mutations in Asf1N, indicating the critical role of salt bridge and van der Waals contacts in the complex formation. Consistently, both of the aforementioned Asf1 mutations also drastically reduced the binding to Cac2C. These results provide a structural basis for a mutually exclusive Asf1-binding model of CAF-1 and HIRA/Hip1, in which Asf1 and CAF-1 assemble histones H3/H4 (H3.1/H4 in vertebrates) in a replication-dependent pathway, whereas Asf1 and HIRA/Hip1 assemble histones H3/H4 (H3.3/H4 in vertebrates) in a replication-independent pathway.