Co-evolution of quaternary organisation and novel RNA tertiary interactions revealed in the crystal structure of a bacterial protein- RNA toxin-antitoxin system
Voss, Jarrod E
Blower, Tim R
Orme, Anastasia L
Whittaker, Tom E
Nucleic Acids Research
Oxford University Press
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Rao, F., Short, F., Voss, J. E., Blower, T. R., Orme, A. L., Whittaker, T. E., Luisi, B., & et al. (2015). Co-evolution of quaternary organisation and novel RNA tertiary interactions revealed in the crystal structure of a bacterial protein- RNA toxin-antitoxin system. Nucleic Acids Research, 43 9529-9540. https://doi.org/10.1093/nar/gkv868
Genes encoding Toxin-Antitoxin (TA) systems are near ubiquitous in bacterial genomes and they play key roles in important aspects of bacterial physiology, including genomic stability, formation of persister cells under antibiotic stress, and resistance to phage infection. The CptIN locus from Eubacterium rectale is a member of the recently-discovered Type III class of TA systems, defined by a protein toxin suppressed by direct interaction with a structured RNA antitoxin. Here, we present the crystal structure of the CptIN protein-RNA complex to 2.2 Å resolution. The structure reveals a new heterotetrameric quaternary organization for the Type III TA class, and the RNA antitoxin bears a novel structural feature of an extended A-twist motif within the pseudoknot fold. The retention of a conserved ribonuclease active site as well as traits normally associated with TA systems, such as plasmid maintenance, implicates a wider functional role for Type III TA systems. We present evidence for the co32 variation of the Type III component pair, highlighting a distinctive evolutionary process in which an enzyme and its substrate co-evolve.
This work was supported by grants from the Biotechnology and Biological Sciences Research Council, United Kingdom (BB/H002677/1 to G.P.C.S and B.F.L.); and the Wellcome Trust, United Kingdom (RG61065 to B.F.L); F.R. was funded by a Biotechnology and Biological Sciences Research Council studentship; F.L.S. held a Commonwealth Scholarship funded by the UK Department for Business, Innovation and Skills and the Cambridge Commonwealth Trust; J.E.V. was funded by a Herschel Smith Scholarship, University of Cambridge, United Kingdom.
External DOI: https://doi.org/10.1093/nar/gkv868
This record's URL: https://www.repository.cam.ac.uk/handle/1810/250315
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/