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Structure and activation mechanism of the yeast RNA Pol II CTD kinase CTDK-1 complex [Biophysics and Computational Biology]
Proceedings of the National Academy of Sciences of the United States of America ( IF 11.1 ) Pub Date : 2021-01-19 , DOI: 10.1073/pnas.2019163118
Yihu Xie 1 , Christopher L Lord 2 , Bradley P Clarke 1 , Austin L Ivey 1 , Pate S Hill 1 , W Hayes McDonald 1, 3 , Susan R Wente 2 , Yi Ren 4
Affiliation  

The C-terminal domain (CTD) kinase I (CTDK-1) complex is the primary RNA Polymerase II (Pol II) CTD Ser2 kinase in budding yeast. CTDK-1 consists of a cyclin-dependent kinase (CDK) Ctk1, a cyclin Ctk2, and a unique subunit Ctk3 required for CTDK-1 activity. Here, we present a crystal structure of CTDK-1 at 1.85-Å resolution. The structure reveals that, compared to the canonical two-component CDK-cyclin system, the third component Ctk3 of CTDK-1 plays a critical role in Ctk1 activation by stabilizing a key element of CDK regulation, the T-loop, in an active conformation. In addition, Ctk3 contributes to the assembly of CTDK-1 through extensive interactions with both Ctk1 and Ctk2. We also demonstrate that CTDK-1 physically and genetically interacts with the serine/arginine-like protein Gbp2. Together, the data in our work reveal a regulatory mechanism of CDK complexes.



中文翻译:

酵母RNA Pol II CTD激酶CTDK-1复合物的结构和激活机制[生物物理学和计算生物学]

C 末端结构域 (CTD) 激酶 I (CTDK-1) 复合物是出芽酵母中的主要 RNA 聚合酶 II (Pol II) CTD Ser2 激酶。CTDK-1 由细胞周期蛋白依赖性激酶 (CDK) Ctk1、细胞周期蛋白 Ctk2 和 CTDK-1 活性所需的独特亚基 Ctk3 组成。在这里,我们展示了 CTDK-1 的晶体结构,分辨率为 1.85-Å。该结构表明,与典型的双组分 CDK-cyclin 系统相比,CTDK-1 的第三个组分 Ctk3 通过稳定 CDK 调节的关键元件 T 环在活性构象中发挥关键作用。 . 此外,Ctk3 通过与 Ctk1 和 Ctk2 的广泛相互作用有助于 CTDK-1 的组装。我们还证明 CTDK-1 在物理和遗传上与丝氨酸/精氨酸样蛋白 Gbp2 相互作用。一起,

更新日期:2021-01-12
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