RT Journal Article
SR Electronic
T1 HORMA domain proteins and a Pch2-like ATPase regulate bacterial cGAS-like enzymes to mediate bacteriophage immunity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 694695
DO 10.1101/694695
A1 Qiaozhen Ye
A1 Rebecca K. Lau
A1 Ian T. Mathews
A1 Jeramie D. Watrous
A1 Camillia S. Azimi
A1 Mohit Jain
A1 Kevin D. Corbett
YR 2019
UL http://biorxiv.org/content/early/2019/07/06/694695.abstract
AB 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 λ 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.