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bioRxiv · 10.1101/694695

HORMA domain proteins and a Pch2-like ATPase regulate bacterial cGAS-like enzymes to mediate bacteriophage immunity

Ye, Q.·Lau, R. K.·Mathews, I. T.·Watrous, J. D.·Azimi, C. S.·Jain, M.·Corbett, K. D.
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Abstract

Bacteria are continually challenged by foreign invaders including bacteriophages, and have evolved a variety of defenses against these invaders. Here, we describe the structural and biochemical mechanisms of a bacteriophage immunity pathway found in a broad array of bacteria, including pathogenic E. coli and Pseudomonas aeruginosa. This pathway employs eukaryotic-like HORMA domain proteins that recognize specific peptides, then bind and activate a cGAS/DncV-like nucleotidyltransferase (CD-NTase) to generate a cyclic tri-AMP (cAAA) second messenger; cAAA in turn activates an endonuclease effector, NucC. Signaling is attenuated by a homolog of the AAA+ ATPase Pch2/TRIP13, which binds and likely disassembles the active HORMA-CD-NTase complex. When expressed in non-pathogenic E. coli, this pathway confers immunity against bacteriophage {lambda} infection. Our findings reveal the molecular mechanisms of a bacterial defense pathway integrating a cGAS-like nucleotidyltransferase with HORMA domain proteins for threat sensing through protein detection, and negative regulation by a Pch2-like ATPase.

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Ye, Q., Lau, R. K., Mathews, I. T., Watrous, J. D., Azimi, C. S., Jain, M., Corbett, K. D.. 2019-07-06. HORMA domain proteins and a Pch2-like ATPase regulate bacterial cGAS-like enzymes to mediate bacteriophage immunity. https://doi.org/10.1101/694695

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