结构导向的 SDS22 与蛋白磷酸酶 PP1 和剪接因子 BCLAF1 相互作用的研究
Structure-Guided Exploration of SDS22 Interactions with Protein Phosphatase PP1 and the Splicing Factor BCLAF1.
机构信息
Laboratory of Biosignaling & Therapeutics, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium; Biomolecular Architecture, Department of Chemistry, KU Leuven, Leuven, Belgium.
Laboratory of Biosignaling & Therapeutics, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
出版信息
Structure. 2019 Mar 5;27(3):507-518.e5. doi: 10.1016/j.str.2018.12.002. Epub 2019 Jan 17.
SDS22 is an ancient regulator of protein phosphatase-1 (PP1). Our crystal structure of SDS22 shows that its twelve leucine-rich repeats adopt a banana-shaped fold that is shielded from solvent by capping domains at its extremities. Subsequent modeling and biochemical studies revealed that the concave side of SDS22 likely interacts with PP1 helices α5 and α6, which are distal from the binding sites of many previously described PP1 interactors. Accordingly, we found that SDS22 acts as a "third" subunit of multiple PP1 holoenzymes. The crystal structure of SDS22 also revealed a large basic surface patch that enables binding of a phosphorylated form of splicing factor BCLAF1. Taken together, our data provide insights into the formation of PP1:SDS22 and the recruitment of additional interaction proteins, such as BCLAF1.
SDS22 是蛋白磷酸酶-1（PP1）的古老调节因子。我们 SDS22 的晶体结构表明，其 12 个富含亮氨酸的重复序列采用香蕉形折叠，其末端的帽状结构将其与溶剂隔离。随后的建模和生化研究表明，SDS22 的凹面可能与远离许多先前描述的 PP1 相互作用蛋白结合位点的 PP1 螺旋 α5 和 α6 相互作用。因此，我们发现 SDS22 作为多种 PP1 全酶的“第三”亚基发挥作用。SDS22 的晶体结构还揭示了一个大的碱性表面斑块，可结合剪接因子 BCLAF1 的磷酸化形式。总之，我们的数据提供了关于 PP1：SDS22 形成和招募额外相互作用蛋白（如 BCLAF1）的见解。
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