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Title: Determinants of eukaryal cell killing by the bacterial ribotoxin PrrC
Authors: Meineke, B.
Schwer, B.
Schaffrath, Raffael
Shuman, S.
First Published: 19-Sep-2010
Publisher: Oxford University Press
Citation: Nucleic Acids Research, 2011, 39 (2), pp. 687-700
Abstract: tRNA damage inflicted by the Escherichia coli anticodon nuclease PrrC (EcoPrrC) underlies an antiviral response to phage T4 infection. PrrC homologs are present in many bacterial proteomes, though their biological activities are uncharted. PrrCs consist of two domains: an N-terminal NTPase module related to the ABC family and a distinctive C-terminal ribonuclease module. In this article, we report that the expression of EcoPrrC in budding yeast is fungicidal, signifying that PrrC is toxic in a eukaryon in the absence of other bacterial or viral proteins. Whereas Streptococcus PrrC is also toxic in yeast, Neisseria and Xanthomonas PrrCs are not. Via analysis of the effects of 118 mutations on EcoPrrC toxicity in yeast, we identified 22 essential residues in the NTPase domain and 11 in the nuclease domain. Overexpressing PrrCs with mutations in the NTPase active site ameliorated the toxicity of wild-type EcoPrrC. Our findings support a model in which EcoPrrC toxicity is contingent on head-to-tail dimerization of the NTPase domains to form two composite NTP phosphohydrolase sites. Comparisons of EcoPrrC activity in a variety of yeast genetic backgrounds, and the rescuing effects of tRNA overexpression, implicate tRNA[superscript: Lys(UUU)] as a target of EcoPrrC toxicity in yeast.
DOI Link: 10.1093/nar/gkq831
ISSN: 0305-1048
eISSN: 1362-4962
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © The Author(s) 2010. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Appears in Collections:Published Articles, Dept. of Genetics

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