A functional association is uncovered between the ribosome-associated trigger factor (TF) chaperone and the ClpXP degradation complex. Bioinformatic analyses demonstrate conservation of the close proximity of tig, the gene coding for TF, and genes coding for ClpXP, suggesting a functional interaction. The effect of TF on ClpXP-dependent degradation varies based on the nature of substrate. While degradation of some substrates are slowed down or are unaffected by TF, surprisingly, TF increases the degradation rate of a third class of substrates. These include λ phage replication protein λO, master regulator of stationary phase RpoS, and SsrA-tagged proteins. Globally, TF acts to enhance the degradation of about 2% of newly synthesized proteins. TF is found to interact through multiple sites with ClpX in a highly dynamic fashion to promote protein degradation. This chaperone-protease cooperation constitutes a unique and likely ancestral aspect of cellular protein homeostasis in which TF acts as an adaptor for ClpXP.
Department of Biochemistry, University of Toronto, Toronto, ON, M5G 1M1, Canada.
Ribosomes, Escherichia coli, Endopeptidase Clp, Peptidylprolyl Isomerase, Peptides, Escherichia coli Proteins, Molecular Chaperones, Viral Proteins, Magnetic Resonance Spectroscopy, Protein Interaction Mapping, Phylogeny, Mutagenesis, Gene Deletion, Binding Sites, Protein Binding, Substrate Specificity, Genome, Bacterial, Models, Biological, Models, Molecular, Protein Multimerization, Proteolysis, Protein Domains