6P8S

Structure of P. aeruginosa ATCC27853 HORMA1:HORMA2:Peptide 1 complex

Summary for 6P8S

• Entry DOI: 10.2210/pdb6p8s/pdb
• Related: 6P8P 6P8R
• Descriptor: HORMA domain containing protein, HORMA1, Peptide 1, ... (7 entities in total)
• Functional Keywords: horma domain, closure motif, cd-ntase, cgas, protein binding
• Biological source: Pseudomonas aeruginosa; More
• Total number of polymer chains: 6
• Total formula weight: 69005.68

Authors

Ye, Q.,Corbett, K.D. (deposition date: 2019-06-07, release date: 2019-12-25, Last modification date: 2023-10-11)

Primary citation

Ye, Q.,Lau, R.K.,Mathews, I.T.,Birkholz, E.A.,Watrous, J.D.,Azimi, C.S.,Pogliano, J.,Jain, M.,Corbett, K.D.
HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-like Enzymes to Mediate Bacteriophage Immunity.
Mol.Cell, 77:709-, 2020

PubMed 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 E. coli and Pseudomonas aeruginosa. This pathway uses eukaryotic-like HORMA domain proteins that recognize specific peptides, then bind and activate a cGAS/DncV-like nucleotidyltransferase (CD-NTase) to generate a cyclic triadenylate (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 disassembles the active HORMA-CD-NTase complex. When expressed in non-pathogenic E. coli, this pathway confers immunity against bacteriophage λ through an abortive infection mechanism. 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 Trip13 ATPase.

PubMed: 31932165
DOI: 10.1016/j.molcel.2019.12.009

Experimental method

X-RAY DIFFRACTION (2 Å)