title: Regulatory role of cardiolipin in the activity of an ATP-dependent protease, Lon, from Escherichia coli.
abstract: Lon is an ATP-dependent serine protease that plays a significant role in the quality control of proteins in cells, degrading misfolded proteins and certain short-lived regulatory proteins under stresses as such heat-shock and UV irradiation. It is known that some polymers containing phosphate groups regulate enzymatic activity by binding with Lon. We focused on the phospholipids of biological membrane components such as phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol and cardiolipin (CL), and examined whether or not liposomes containing these phospholipids regulate the enzymatic activity of Lon. CL-containing liposomes specifically inhibited both the proteolytic and ATPase activities of Lon in a dose-dependent manner. In addition, on pull-down assay, we found that CL-containing liposomes selectively bound to Lon. The interaction between CL-containing liposomes and Lon changed with the order of addition of Mg(2+)/ATP. When CL-containing liposomes were added after the addition of Mg(2+)/ATP to Lon, the binding of CL-containing liposomes to Lon was significantly decreased as compared with the reversed order. In fact, we found that CL-containing liposomes bound to Lon, resulting in inhibition of the enzymatic activity of Lon. These results suggest that Lon interacts with CL in biological membranes, which may regulate the functions of Lon as a protein-degrading centre in accordance with environmental changes inside cells.
authors: Laboratory of Biodefense and Regulation, Graduate School of Pharmaceutical Sciences, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors: Noriko
authors: N
authors: Minami
authors: Tatsuji
authors: T
authors: Yasuda
authors: Yoshiyuki
authors: Y
authors: Ishii
authors: Ko
authors: K
authors: Fujimori
authors: Fumio
authors: F
authors: Amano
mesh_terms: D002308:Cardiolipins / Q000235:genetics / Q000378:metabolism*; D002364:Caseins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D049070:Protease La / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D002308:Cardiolipins; D002364:Caseins; D029968:Escherichia coli Proteins; D008081:Liposomes; D010743:Phospholipids; C483567:Lon protein, E coli; D049070:Protease La