Structural similarities and functional differences clarify evolutionary relationships between tRNA healing enzymes and the myelin enzyme CNPase
|Author:||Muruganandam, Gopinath1; Raasakka, Arne2,3; Myllykoski, Matti2;|
1Centre for Structural Systems Biology - Helmholtz Centre for Infection Research, German Electron Synchrotron (DESY)
2Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu
3Department of Biomedicine, University of Bergen
|Online Access:||PDF Full Text (PDF, 2.7 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe201708218170
|Publish Date:|| 2017-08-21
Background: Eukaryotic tRNA splicing is an essential process in the transformation of a primary tRNA transcript into a mature functional tRNA molecule. 5′-phosphate ligation involves two steps: a healing reaction catalyzed by polynucleotide kinase (PNK) in association with cyclic phosphodiesterase (CPDase), and a sealing reaction catalyzed by an RNA ligase. The enzymes that catalyze tRNA healing in yeast and higher eukaryotes are homologous to the members of the 2H phosphoesterase superfamily, in particular to the vertebrate myelin enzyme 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase).
Results: We employed different biophysical and biochemical methods to elucidate the overall structural and functional features of the tRNA healing enzymes yeast Trl1 PNK/CPDase and lancelet PNK/CPDase and compared them with vertebrate CNPase. The yeast and the lancelet enzymes have cyclic phosphodiesterase and polynucleotide kinase activity, while vertebrate CNPase lacks PNK activity. In addition, we also show that the healing enzymes are structurally similar to the vertebrate CNPase by applying synchrotron radiation circular dichroism spectroscopy and small-angle X-ray scattering.
Conclusions: We provide a structural analysis of the tRNA healing enzyme PNK and CPDase domains together. Our results support evolution of vertebrate CNPase from tRNA healing enzymes with a loss of function at its N-terminal PNK-like domain.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This study has been supported by the Academy of Finland, the German Federal Ministry for Education and Research, and the Research and Science Foundation of the City of Hamburg (Germany). The funders had no role in the design of the study, the collection, analysis, and interpretation of data, or in writing the manuscript.
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