Hee Jong Kim, Mary R. Szurgot, Trevor van Eeuwen, M. Daniel Ricketts, Pratik Basnet, Athena L. Zhang, Austin Vogt, Samah Sharmin, Craig D. Kaplan, Benjamin A. Garcia, Ronen Marmorstein, Kenji Murakami
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引用次数: 0
摘要
进化保守的HIRA/Hir组蛋白伴侣复合体和ASF1a/Asf1协同伴侣合作，将组蛋白（H3/H4）2四聚体沉积在DNA上，进行不依赖复制的染色质组装。HIRA/Hir 复合物的分子结构及其组蛋白沉积模式一直不为人知。在这里，我们以 2.9-6.8 Å 的分辨率报告了 S. cerevisiae Hir 与 Asf1/H3/H4 复合物的冷冻电镜结构。我们发现，Hir 复合物形成一个弧形二聚体，Hir1/Hir2/Hir3/Hpc2 的化学计量为 2/4/2/4。复合物的核心包含两个 Hir1/Hir2/Hir2 三聚体和 Hir3 的 N 端片段，形成一个包含两个 Hpc2 副本的中心空腔，其中一个由 Asf1/H3/H4 参与，处于可容纳组蛋白 (H3/H4)2 四聚体的合适位置，而 Hir3 的 C 端片段具有核酸结合活性，可将 DNA 包裹在 Hpc2 辅助的组蛋白四聚体周围。该结构为 Hir/Asf1 复合物如何促进组蛋白四聚体的形成并随后将其沉积到 DNA 上提供了一个模型。
The evolutionarily conserved HIRA/Hir histone chaperone complex and ASF1a/Asf1 co-chaperone cooperate to deposit histone (H3/H4)2 tetramers on DNA for replication-independent chromatin assembly. The molecular architecture of the HIRA/Hir complex and its mode of histone deposition have remained unknown. Here, we report the cryo-EM structure of the S. cerevisiae Hir complex with Asf1/H3/H4 at 2.9–6.8 Å resolution. We find that the Hir complex forms an arc-shaped dimer with a Hir1/Hir2/Hir3/Hpc2 stoichiometry of 2/4/2/4. The core of the complex containing two Hir1/Hir2/Hir2 trimers and N-terminal segments of Hir3 forms a central cavity containing two copies of Hpc2, with one engaged by Asf1/H3/H4, in a suitable position to accommodate a histone (H3/H4)2 tetramer, while the C-terminal segments of Hir3 harbor nucleic acid binding activity to wrap DNA around the Hpc2-assisted histone tetramer. The structure suggests a model for how the Hir/Asf1 complex promotes the formation of histone tetramers for their subsequent deposition onto DNA.
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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