# Bacterial immune activation via supramolecular assembly with phage triggers

## TL;DR

Bacteria defend against phages by forming large ring structures that activate an immune protein called RAZR, which then inhibits phage replication.

## Contribution

The paper reveals a novel mechanism where RAZR is activated by recognizing phage proteins that form specific ring geometries.

## Key findings

- RAZR assembles into a 24-meric ring around phage proteins to cleave RNA and restrict phage propagation.
- Phage proteins with similar ring diameters trigger RAZR activation, suggesting geometry is crucial for function.
- The absence of such structures in uninfected cells prevents unintended RAZR activation and auto-immunity.

## Abstract

Bacteria use diverse mechanisms to protect themselves against phages1–6. Many antiphage systems form large oligomeric complexes, but how oligomerization is regulated during phage infection remains mostly unknown7–12. Here we demonstrate that the bacterial immunity protein ring-activated zinc-finger RNase (RAZR) assembles into an active, 24-meric ring around the circumference of large ring structures formed by two unrelated phage proteins: a putative recombinase and a portal protein. Each multi-layered, megadalton-scale complex enables RAZR to cleave RNA nonspecifically to inhibit translation and restrict phage propagation. The recognition of unrelated phage proteins that form rings with similar diameters indicates that these proteins not only bind to RAZR but also enforce a geometry crucial to activation. The lack of large ring structures in the host probably prevents auto-immunity and RAZR activation before infection. The infection-triggered oligomerization of RAZR mirrors pathogen-induced oligomerization in eukaryotic innate immune complexes13, underscoring a common principle of immunity across biology.

An antiphage defence system has an activation mechanism that relies on the sensing of phage-encoded proteins that enforce geometry crucial to activation and are not typically present in non-infected cells.