Structural basis for origin recognition complex 1 protein-silence information regulator 1 protein interaction in epigenetic silencing
Structural basis for origin recognition complex 1 protein-silence information regulator 1 protein interaction in epigenetic silencing
复制标题
DOI：
10.1073/pnas.0502946102
复制
发表时间：
2005-06-14
影响因子：
11.1
通讯作者：
Xu, RM
中科院分区：
文献类型：
--
作者：
Hsu, HC;Stillman, B;Xu, RM
沉默信息调节蛋白1(Sir1p)与起源识别复合体最大亚基--起源识别复合体1蛋白(Orc1p)之间的相互作用在酿酒酵母隐性交配型基因座转录沉默的建立中起着重要作用。Sir1p与Orc1p的N-末端结合，包含一个溴相邻同源(BAH)结构域，在各种染色质相关蛋白中发现。为了了解SIR蛋白募集的分子机制，我们确定了Orc1p的N端结构域与Sir1p的Orc1p相互作用结构域的2.5埃共晶结构。该结构揭示了Sir1p Orc1p相互作用结构域具有双叶结构：一个类似都铎结构域王室家族折叠的α/βN-末端叶和一个C-末端叶。Sir1p的N-末端叶结合在Orc1p的螺旋亚区和BAH结构域之间的浅槽中。该结构提供了对Orc1p-Sir1p相互作用特异性的机制理解，以及对涉及BAH结构域的蛋白质-蛋白质相互作用的洞察。
The interaction between silence information regulator 1 protein (Sir1p) and origin recognition complex 1 protein (Orc1p), the largest subunit of the origin recognition complex, plays an important role in the establishment of transcriptional silencing at the cryptic mating-type gene loci in Saccharomyces cerevisiae. Sir1p binds the N-terminal region of Orc1p encompassing a Bromo-adjacent homology (BAH) domain found in various chromatin-associated proteins. To understand the molecular mechanism of Sir protein recruitment, we have determined a 2.5-angstrom cocrystal structure of the N-terminal domain of Orc1p in complex with the Orc1p-interacting domain of Sir1p. The structure reveals that Sir1p Orc1p-interacting domain has a bilobal structure: an alpha/beta N-terminal lobe and a C-terminal lobe resembling the Tudor domain royal family fold. The N-terminal lobe of Sir1p binds in a shallow groove between a helical subdomain and the BAH domain of Orc1p. The structure provides a mechanistic understanding of Orc1p-Sir1p interaction specificity, as well as insights into protein-protein interactions involving BAH domains in general.