Rizzolo K, Yu AYH, Ologbenla A, Kim SR, Zhu H, Ishimori K, Thibault G, Leung E, Zhang YW, Teng M, Haniszewski M, Miah N, Phanse S, Minic Z, Lee S, Caballero JD, Babu M, Tsai FTF, Saio T, Houry WA.

In this manuscript, Walid A. Houry’s group identified a potential co-translational degradation pathway in Gram negative bacteria. A functional association was uncovered between the ribosome-associated trigger factor (TF) chaperone and the ClpXP degradation complex. Bioinformatic analyses demonstrated conservation of the close proximity of tig, gene coding for TF, and genes coding for ClpXP suggesting a functional interaction. Effect of TF on ClpXP-dependent degradation varied based on the nature of substrate. While degradation of some substrates was slowed down or was unaffected by TF, surprisingly, TF increased 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 was found to act to enhance the degradation of about 2% of newly synthesized proteins. TF was 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 that likely leads to co-translational degradation.

Nature Communications. 2021;12(1):281. doi: 10.1038/s41467-020-20553-x. PMID: 33436616