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

J Biol Chem

Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada; Department of Chemistry, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Published: April 2024

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11002289PMC
http://dx.doi.org/10.1016/j.jbc.2024.107165DOI Listing

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