Toxic antiphage defense proteins inhibited by intragenic antitoxin proteins
Aoshu Zhong, Xiaofang Jiang, Alison B. Hickman, Katherine Klier, Gabriella I. C. Teodoro, Fred Dyda, Michael T. Laub, Gisela Storz
Abstract
Recombination-promoting nuclease (Rpn) proteins are broadly distributed across bacterial phyla, yet their functions remain unclear. Here, we report that these proteins are toxin–antitoxin systems, comprised of genes-within-genes, that combat phage infection. We show the small, highly variable Rpn C -terminal domains (Rpn S ), which are translated separately from the full-length proteins (Rpn L ), directly block the activities of the toxic Rpn L . The crystal structure of RpnA S revealed a dimerization interface encompassing α helix that can have four amino acid repeats whose number varies widely among strains of the same species. Consistent with strong selection for the variation, we document that plasmid-encoded RpnP2 L protects Escherichia coli against certain phages. We propose that many more intragenic-encoded proteins that serve regulatory roles remain to be discovered in all organisms.