# A comprehensive catalogue of receptor-binding domains in extracellular contractile injection systems

## TL;DR

This study explores the diversity and function of receptor-binding domains in extracellular contractile injection systems, revealing their potential to target various cells and deliver toxins.

## Contribution

The paper introduces a comprehensive analysis of eCIS tail fiber proteins, identifying new structural clusters and their potential binding targets.

## Key findings

- Identified 3445 eCIS tail fiber proteins across 1069 microbes, categorized by five new N-terminal domains.
- Classified fibers into 276 structural clusters and 1177 domain fold families, likely involved in cell surface binding.
- Experimentally demonstrated that a Paenibacillus eCIS tail fiber can bind and direct effector injection into human monocyte-like cells.

## Abstract

Extracellular contractile injection systems (eCISs) are bacteriophage tail-derived toxin delivery complexes in prokaryotes. They play roles in microbial interactions with hosts, using tail fiber proteins for target cell binding. Here, we present a comprehensive analysis of eCIS tail fiber genes in bacterial and archaeal genomes, providing insights into their remarkable diversity, target cells, functional adaptations, and evolutionary dynamics. We identified 3445 eCIS tail fiber proteins encoded in 2585 eCIS loci from 1069 microbes. These fibers can be categorized by five new N-terminal domains responsible for tail fiber attachment to eCIS baseplates. We use structure prediction to classify fibers into 276 structural clusters and 1177 domain fold families, which likely mediate glycan and protein binding on the cell surface of eukaryotes or bacterial targets. DNA sequences encoding these rapidly evolving domains may have been acquired from diverse eukaryotes, bacteria, and viruses. Finally, we experimentally show that a candidate tail fiber from a Paenibacillus eCIS can bind and direct effector injection into THP-1 human monocyte-like cells, possibly binding D-mannose on the cell surface. This study reveals the exceptional diversity of eCIS receptor binding domains, suggests new eCIS target cells, and provides thousands of proteins that can adhere to different cell types.

Extracellular contractile injection systems (eCISs) are bacteriophage tail-derived toxin delivery complexes that are present in many prokaryotes. Here, the authors present an analysis of eCIS tail fiber genes in bacterial and archaeal genomes, providing insights into their diversity, target cells, functional adaptations, and evolutionary dynamics.