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Thermodynamic profiles for cotranslational trigger factor substrate recognition
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DOI：10.1126/sciadv.adn4824.png)
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Abstract
En 中文
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 life cycle and has a ubiquitous role as the first chaperone encountered by proteins during synthesis. However, our understanding of how TF achieves favorable 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 enthalpy-driven, with micromolar affinity, while nanomolar affinity is achieved through a favorable entropic contribution for both intrinsically disordered and folding-competent nascent chains. These findings suggest a general mechanism for cotranslational TF function, which relies on occupation of the exposed TF-substrate binding groove rather than specific complementarity between chaperone and nascent chain. These insights add to our wider understanding of how proteins can achieve broad substrate specificity.
Keywords:
NASCENT CHAIN
RIBOSOME
PROTEIN
COMPLEXES
DYNAMICS
STRATEGY
REVEALS
DNAK
COLI
Journal
IF:
12.5
Papers:
2.0W
Citations:
18.1W