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DYW domain structures imply an unusual regulation principle in plant organellar RNA editing catalysis
Nature Catalysis ( IF 37.8 ) Pub Date : 2021-06-21 , DOI: 10.1038/s41929-021-00633-x
Mizuki Takenaka 1 , Sachi Takenaka 1, 2 , Tatjana Barthel 2, 3, 4 , Brody Frink 1 , Sascha Haag 5 , Daniil Verbitskiy 5 , Bastian Oldenkott 6 , Mareike Schallenberg-Rüdinger 6 , Christian G Feiler 7 , Manfred S Weiss 7 , Gottfried J Palm 3 , Gert Weber 7
Affiliation  

RNA editosomes selectively deaminate cytidines to uridines in plant organellar transcripts—mostly to restore protein functionality and consequently facilitate mitochondrial and chloroplast function. The RNA editosomal pentatricopeptide repeat proteins serve target RNA recognition, whereas the intensively studied DYW domain elicits catalysis. Here we present structures and functional data of a DYW domain in an inactive ground state and activated. DYW domains harbour a cytidine deaminase fold and a C-terminal DYW motif, with catalytic and structural zinc atoms, respectively. A conserved gating domain within the deaminase fold regulates the active site sterically and mechanistically in a process that we termed gated zinc shutter. Based on the structures, an autoinhibited ground state and its activation are cross-validated by RNA editing assays and differential scanning fluorimetry. We anticipate that, in vivo, the framework of an active plant RNA editosome triggers the release of DYW autoinhibition to ensure a controlled and coordinated cytidine deamination playing a key role in mitochondrial and chloroplast homeostasis.



中文翻译:

DYW结构域结构暗示植物细胞器RNA编辑催化中的一种不寻常的调控原理

RNA 编辑体选择性地将植物细胞器转录物中的胞苷脱氨基成尿苷——主要是为了恢复蛋白质功能,从而促进线粒体和叶绿体功能。RNA 编辑体五肽重复蛋白服务于目标 RNA 识别,而深入研究的 DYW 结构域引发催化。在这里,我们展示了处于非活动基态和激活状态的 DYW 域的结构和功能数据。DYW 结构域具有胞苷脱氨酶折叠和 C 末端 DYW 基序,分别具有催化和结构锌原子。在我们称为门控锌快门的过程中,脱氨酶折叠内的保守门控域在空间和机械上调节活性位点。基于结构,一种自身抑制的基态及其激活通过 RNA 编辑测定和差示扫描荧光法进行交叉验证。我们预计,在体内,活性植物 RNA 编辑体的框架会触发 DYW 自身抑制的释放,以确保受控和协调的胞苷脱氨在线粒体和叶绿体稳态中起关键作用。

更新日期:2021-06-21
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