A Peptide Signal for Adapter Protein-Mediated Degradation by the AAA+ Protease ClpCP

SummaryComS is an antiadaptor protein that binds to MecA, displacing the competence transcription factor ComK. This protects ComK from degradation by the ClpCP protease and turns on the switch leading to bistable gene expression. Here we identify the motifs on ComK and ComS that mediate binding to MecA, and we show that they contain similar core sequences (FMLYPK and IILYPR, respectively), located near the C and N termini of the respective proteins. A 17 residue peptide from ComK including this sequence has the same affinity for MecA as full-length ComK, and a peptide containing this sequence is sufficient to target green fluorescent protein for degradation in vivo. Crosslinking and competition experiments demonstrate that ComK- and ComS-derived peptides bind to the same region of MecA. We propose a model in which the antiadaptor protein ComS acts by direct competition to protect ComK from degradation.