ClpS, a Substrate Modulator of the ClpAP Machine

• Published in: Molecular cell 2002-03, Vol.9 (3), p.673-683
• Main Authors: Dougan, David A, Reid, Brian G, Horwich, Arthur L, Bukau, Bernd
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Amino Acid Sequence; Carrier Proteins - genetics; Carrier Proteins - metabolism; Endopeptidase Clp; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Hot Temperature; Luciferases - metabolism; Malate Dehydrogenase - metabolism; Molecular Sequence Data; Operon - genetics; Protein Binding; RNA, Bacterial - metabolism; Sequence Alignment; Serine Endopeptidases - genetics; Serine Endopeptidases - metabolism; Substrate Specificity
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(02)00485-9

In the bacterial cytosol, ATP-dependent protein degradation is performed by several different chaperone-protease pairs, including ClpAP. The mechanism by which these machines specifically recognize substrates remains unclear. Here, we report the identification of a ClpA cofactor from Escherichia coli, ClpS, which 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. In contrast, ClpS enhanced ClpA recognition of two heat-aggregated proteins in vitro and, consequently, the ClpAP-mediated disaggregation and degradation of these substrates. We conclude that ClpS modifies ClpA substrate specificity, potentially redirecting degradation by ClpAP toward aggregated proteins.