Structural basis for sequence-dependent recognition of colicin E5 tRNase by mimicking the mRNA–tRNA interaction

Colicin E5—a tRNase toxin—specifically cleaves QUN (Q: queuosine) anticodons of the Escherichia coli tRNAs for Tyr, His, Asn and Asp. Here, we report the crystal structure of the C-terminal ribonuclease domain (CRD) of E5 complexed with a substrate analog, namely, dGpdUp, at a resolution of 1.9 Å. T...

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Main Authors: Yajima, Shunsuke, Inoue, Sakura, Ogawa, Tetsuhiro, Nonaka, Takamasa, Ohsawa, Kanju, Masaki, Haruhiko
Formato: Artigo
Idioma:English
Publicado em: Oxford University Press 2006
Assuntos:
Structural Biology
Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC1669751/
https://ncbi.nlm.nih.gov/pubmed/17099236
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1093/nar/gkl729
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Resumo:Colicin E5—a tRNase toxin—specifically cleaves QUN (Q: queuosine) anticodons of the Escherichia coli tRNAs for Tyr, His, Asn and Asp. Here, we report the crystal structure of the C-terminal ribonuclease domain (CRD) of E5 complexed with a substrate analog, namely, dGpdUp, at a resolution of 1.9 Å. Thisstructure is the first to reveal the substrate recognition mechanism of sequence-specific ribonucleases. E5-CRD realized the strict recognition for both the guanine and uracil bases of dGpdUp forming Watson–Crick-type hydrogen bonds and ring stacking interactions, thus mimicking the codons of mRNAs to bind to tRNA anticodons. The docking model of E5-CRD with tRNA also suggests its substrate preference for tRNA over ssRNA. In addition, the structure of E5-CRD/dGpdUp along with the mutational analysis suggests that Arg33 may play an important role in the catalytic activity, and Lys25/Lys60 may also be involved without His in E5-CRD. Finally, the comparison of the structures of E5-CRD/dGpdUp and E5-CRD/ImmE5 (an inhibitor protein) complexes suggests that the binding mode of E5-CRD and ImmE5 mimics that of mRNA and tRNA; this may represent the evolutionary pathway of these proteins from the RNA–RNA interaction through the RNA–protein interaction of tRNA/E5-CRD.