Dilworth David, Upadhyay Santosh K, Bonnafous Pierre, Edoo Amiirah Bibi, Bourbigot Sarah, Pesek-Jardim Francy, Gudavicius Geoff, Serpa Jason J, Petrotchenko Evgeniy V, Borchers Christoph H, Nelson Christopher J, Mackereth Cameron D
Dept. of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8W 3P6, Canada.
Univ. Bordeaux, Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, F-33607 Pessac, France.
Nucleic Acids Res. 2017 Nov 16;45(20):11989-12004. doi: 10.1093/nar/gkx852.
Prolyl isomerases are defined by a catalytic domain that facilitates the cis-trans interconversion of proline residues. In most cases, additional domains in these enzymes add important biological function, including recruitment to a set of protein substrates. Here, we report that the N-terminal basic tilted helix bundle (BTHB) domain of the human prolyl isomerase FKBP25 confers specific binding to double-stranded RNA (dsRNA). This binding is selective over DNA as well as single-stranded oligonucleotides. We find that FKBP25 RNA-association is required for its nucleolar localization and for the vast majority of its protein interactions, including those with 60S pre-ribosome and early ribosome biogenesis factors. An independent mobility of the BTHB and FKBP catalytic domains supports a model by which the N-terminus of FKBP25 is anchored to regions of dsRNA, whereas the FKBP domain is free to interact with neighboring proteins. Apart from the identification of the BTHB as a new dsRNA-binding module, this domain adds to the growing list of auxiliary functions used by prolyl isomerases to define their primary cellular targets.
脯氨酰异构酶由一个催化结构域定义，该结构域促进脯氨酸残基的顺反异构化。在大多数情况下，这些酶中的其他结构域增加了重要的生物学功能，包括募集到一组蛋白质底物上。在这里，我们报告人类脯氨酰异构酶FKBP25的N端碱性倾斜螺旋束（BTHB）结构域赋予其与双链RNA（dsRNA）的特异性结合。这种结合对DNA以及单链寡核苷酸具有选择性。我们发现FKBP25与RNA的结合是其核仁定位以及绝大多数蛋白质相互作用所必需的，包括与60S前核糖体和早期核糖体生物发生因子的相互作用。BTHB和FKBP催化结构域的独立移动性支持了一种模型，即FKBP25的N端锚定在dsRNA区域，而FKBP结构域则可自由与相邻蛋白质相互作用。除了将BTHB鉴定为一种新的dsRNA结合模块外，该结构域还增加了脯氨酰异构酶用于定义其主要细胞靶点的辅助功能的清单。
