Determinants of eukaryal cell killing by the bacterial ribotoxin PrrC Journal Article

   

Authors:	Meineke, B.; Schwer, B.; Schaffrath, R.; Shuman, S.
Article Title:	Determinants of eukaryal cell killing by the bacterial ribotoxin PrrC
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 tRNALys(UUU) as a target of EcoPrrC toxicity in yeast. © 2010 The Author(s).
Journal Title:	Nucleic Acids Research
Volume:	39
Issue:	2
ISSN:	0305-1048
Publisher:	Oxford University Press
Date Published:	2011-01-01
Start Page:	687
End Page:	700
Language:	English
DOI:	10.1093/nar/gkq831
PROVIDER:	scopus
PMCID:	PMC3025547
PUBMED:	20855293
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-79551482322&partnerID=40&md5=bd651d0c9cae8cd3a40cb421763eabae
Notes:	--- - "Export Date: 4 March 2011" - "CODEN: NARHA" - "Source: Scopus"

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