Structural basis of the Sir1-origin recognition complex interaction in transcriptional silencing
Structural basis of the Sir1-origin recognition complex interaction in transcriptional silencing
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DOI：
10.1073/pnas.0503525102
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发表时间：
2005-06-14
影响因子：
11.1
通讯作者：
Keck, JL
中科院分区：
文献类型：
--
作者：
Hou, ZG;Bernstein, DA;Keck, JL
Sir 1蛋白通过与origin recognition complex（ORC）的Orc 1 p亚基的溴邻同源（BAH）结构域相互作用，在酿酒酵母（Saccharomyces cerevisiae）的隐蔽交配型位点HMR和HML上建立沉默的染色质结构中发挥关键作用。在这里，我们提出了高分辨率的晶体结构的ORC相互作用区域（OIR）的Sir 1 p和OIR和BAH域之间形成的复合物。OIR内的氨基酸先前被证明是需要一个Sir 1 p/ORC相互作用的保守，凸表面上，形成一个互补的界面与凹区的Orc 1 BAH结构域，这是转录沉默的关键。OIR/BAH相互作用表面包括每个蛋白质中离散结构模块之间的疏水性和极性/离子相互作用的网络，并且涉及先前研究中未涉及的几个残基。这些数据提供了重要的结构洞察蛋白质-蛋白质相互作用的形成一个专门的染色质结构域内真核细胞染色体的关键。
The Sir1 protein plays a key role in establishing a silent chromatin structure at the cryptic mating-type loci HMR and HML in Saccharomyces cerevisiae by interacting with the bromo-adjacent homology (BAH) domain of the Orc1p subunit of the origin recognition complex (ORC). Here, we present the high-resolution crystal structures of the ORC interaction region (OIR) of Sir1p and that of the complex formed between the OIR and BAH domains. Amino acids within the OIR previously shown to be required for a Sir1p/ORC interaction are presented on a conserved, convex surface that forms a complementary interface with a concave region of the Orc1 BAH domain that is critical for transcriptional silencing. The OIR/BAH interaction surface comprises a network of hydrophobic and polar/ionic interactions between discrete structural modules in each protein and involves several residues that were not implicated in previous studies. These data provide important structural insights into a protein-protein interaction critical for the formation of a specialized chromatin domain within eukaryotic chromosomes.