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Thermodynamic profiles for co-translational trigger factor function

Herling, T. W.; Cassaignau, A. M. E.; Wentink, A. S.; Peter, Q. A. E.; Kumar, P. C.; Kartanas, T.; Schneider, M. M.; Cabrita, L. D.; Christodoulou, J.; Knowles, T. P. J.

2023-08-24 biophysics
10.1101/2023.08.23.554456 bioRxiv
Show abstract

Molecular chaperones are central to the maintenance of proteostasis in living cells. A key member of this protein family is trigger factor (TF), which acts throughout the protein lifecycle and has a ubiquitous role as the first chaperone encountered by proteins during synthesis. However, our understanding of how TF achieves favourable interactions with such a diverse substrate base remains limited. Here, we use microfluidics to reveal the thermodynamic determinants of this process. We find that TF binding to empty 70S ribosomes is enthalpydriven, with micromolar affinity, while nanomolar affinity is achieved through a favourable entropic contribution for both intrinsically disordered and folding competent nascent chains. These findings suggest a general mechanism for co-translational TF function, which relies on occupation of the exposed TF substrate-binding groove, rather than specific complementarity between chaperone and RNC. These insights add to our wider understanding of how proteins can achieve broad substrate specificity.

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