Functional Cooperativity Between the Trigger Factor Chaperone and the ClpXP Degradation System

Abstract

Comprehensive bioinformatic analyses demonstrated the conservation of the close proximity of the tig gene coding for the ribosome‐associated chaperone trigger factor (TF) chaperone and the genes coding for the ClpXP proteolytic complex suggesting the possible functional association between the protein folding and the protein degradation systems. Genome‐wide genetic interaction studies further supported such an observation. The effect of TF on ClpXP‐dependent degradation varied depending on the nature of the substrate. For some substrates, TF slowed down their degradation by ClpXP, while for others it had no effect. Surprisingly, for a third class of substrates, TF increased the degradation rate. The ClpXP‐dependent degradation of the λ phage replication protein λO was significantly enhanced by TF in vitro and in vivo. TF was found to interact with both ClpX and λO with similar affinities and to enhance the ClpXP‐mediated degradation of ribosome‐stalled λO nascent chains. Experiments suggest that TF transfers λO to ClpX for eventual degradation by the ClpP serine protease and that this could occur cotranslationally. Globally, it is estimated that TF enhances the degradation of about 2% of newly synthesized E. coli proteins. This reveals a new role for TF in facilitating the degradation of newly translated proteins and the potential presence of cotranslational degradation in bacteria.Support or Funding InformationCanadian Institutes of Health Research