title: Lon and Clp family proteases and chaperones share homologous substrate-recognition domains.
abstract: Lon protease and members of the Clp family of molecular chaperones and protease regulatory subunits contain homologous regions with properties expected for substrate-binding domains. Fragments corresponding to these sequences are stably and independently folded for Lon, ClpA, and ClpY. The corresponding regions from ClpB and ClpX are unstable. All five fragments exhibit distinct patterns of binding to three proteins that are protease substrates in vivo: the heat shock transcription factor sigma32, the SOS mutagenesis protein UmuD, and Arc repressor bearing the SsrA degradation tag. Recognition of UmuD is mediated through peptide sequences within a 24-residue N-terminal region whereas recognition of both sigma32 and SsrA-tagged Arc requires sequences at the C terminus. These results indicate that the Lon and Clp proteases use the same mechanism of substrate discrimination and suggest that these related ATP-dependent bacterial proteases scrutinize accessible or disordered regions of potential substrates for the presence of specific targeting sequences.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Smith
authors.forename: T A
authors.initials: TA
authors.lastname: Baker
authors.forename: R T
authors.initials: RT
authors.lastname: Sauer
mesh_terms: D049069:ATP-Dependent Proteases; D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins; D001665:Binding Sites / Q000235:genetics; D049071:Endopeptidase Clp; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D049070:Protease La; D017510:Protein Folding; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; C483566:ClpYQ protease, E coli; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D049069:ATP-Dependent Proteases; D012697:Serine Endopeptidases; C483568:ClpA protease, E coli; C483567:Lon protein, E coli; D049070:Protease La; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases