# Target-locked: A mechanism for disaggregase binding to aggregated proteins

## TL;DR

This paper explains how ClpG, a protein in Pseudomonas aeruginosa, targets and breaks apart damaged proteins during heat stress.

## Contribution

The study reveals a new mechanism where ClpG uses multiple subunits to bind to aggregated proteins via hydrophobic interactions.

## Key findings

- ClpG uses N-terminal hydrophobic residues on a β-sheet loop to bind aggregated proteins.
- Four or more ClpG subunits are required for effective substrate binding.
- The mechanism is based on avidity, allowing multiple interactions with hydrophobic patches.

## Abstract

ClpG is a novel autonomous disaggregase found in Pseudomonas aeruginosa that confers resistance to lethal heat stress. The mechanism by which ClpG specifically targets protein aggregates for disaggregation is unknown. In their recent work published in JBC, Katikaridis et al. (2023) identify an avidity-based mechanism by which four or more ClpG subunits, through specific N-terminal hydrophobic residues located on an exposed β-sheet loop, interact with multiple hydrophobic patches on an aggregated protein substrate. This study establishes a model for substrate binding to a prokaryotic disaggregase that should inform further investigations into other autonomous disaggregases.