[1] ClpS interacts with protein substrates that have a bulky hydrophobic residue (leucine, phenylalanine, tyrosine, and tryptophan) at the N-terminus.

In the bacterial cytosol, ATP-dependent protein degradation is performed by several different chaperone-protease pairs, including ClpAP.

ClpS directly influences the ClpAP machine by binding to the N-terminal domain of the chaperone ClpA.

The degradation of ClpAP substrates, both SsrA-tagged proteins and ClpA itself, is specifically inhibited by ClpS.

ClpS modifies ClpA substrate specificity, potentially redirecting degradation by ClpAP toward aggregated proteins.