5'-diphosphate-guanosine-3'-diphosphate (ppGpp) stimulates the degradation of certain proteins by ATP-dependent protease La from Escherichia coli

Abstract

During starvation, Escherichia coli increase their rate of breakdown of pre-existing cell proteins from 2- to 4-fold. This response requires ATP and an accumulation of 5'-diplios-phate-guanosine-3'-diphosphate (ppGpp). Addition of ppGpp to protease La together with ATP was found to stimulate 3- to 10-fold the hydrolysis of casein or globin whose carboxyl groups were derivatized with ethylene diamine (AEA-casein). Under these conditions, the hydrolysis of ATP by protease La increased about 2-fold. ppGpp was effective at levels (0.5-3 mM) found in vivo during starvation. It showed, however, little or no effect on the hydrolysis of AEA-casein by other soluble proteases in E. coli. Certain related nucleotides, including 5’-triphosphate-guanosine-3'-diphosphate (pppGpp), 5'-diphosphate- guanosine-3'-monophosphate (ppGp) and 5’-diphosphate-adenosine- 노-diphosphate (ppApp), that are also found in starving bacteria, showed similar effects. This ability of ppGpp to enhance hydrolysis of certain model polypeptides by protease La may contribute to the accelerated degradation of specific proteins during starvation. However, Ion mutants defective in this enzyme still can enhance overall proteolysis during glucose or nitrogen deprivation.