title: ClpS, a substrate modulator of the ClpAP machine.
abstract: 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.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Freiburg, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany. dougan@biochemie.uni-freiburg.de
authors.forename: David A
authors.initials: DA
authors.lastname: Dougan
authors.forename: Brian G
authors.initials: BG
authors.lastname: Reid
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Horwich
authors.forename: Bernd
authors.initials: B
authors.lastname: Bukau
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D049071:Endopeptidase Clp; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D008156:Luciferases / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008969:Molecular Sequence Data; D009876:Operon / Q000235:genetics*; D011485:Protein Binding; D012329:RNA, Bacterial / Q000378:metabolism; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D002352:Carrier Proteins; C454820:ClpS protein, E coli; D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; C096222:tmRNA; D008291:Malate Dehydrogenase; D008156:Luciferases; D012697:Serine Endopeptidases; C483568:ClpA protease, E coli; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases