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GROEL/ES Buffers Entropic Traps in Folding Pathway during Evolution of a Model Substrate
Sadat A., Tiwari S., Verma K., Ray A., Ali M., Upadhyay V., Singh A., Chaphalkar A., Ghosh A., Chakraborty R.Show More
Published in Academic Press
PMID: 32835659
Volume: 432
Issue: 20
Pages: 5649 - 5664
The folding landscape of proteins can change during evolution with the accumulation of mutations that may introduce entropic or enthalpic barriers in the protein folding pathway, making it a possible substrate of molecular chaperones in vivo. Can the nature of such physical barriers of folding dictate the feasibility of chaperone-assistance? To address this, we have simulated the evolutionary step to chaperone-dependence keeping GroEL/ES as the target chaperone and GFP as a model protein in an unbiased screen. We find that the mutation conferring GroEL/ES dependence in vivo and in vitro encode an entropic trap in the folding pathway rescued by the chaperonin. Additionally, GroEL/ES can edit the formation of non-native contacts similar to DnaK/J/E machinery. However, this capability is not utilized by the substrates in vivo. As a consequence, GroEL/ES caters to buffer mutations that predominantly cause entropic traps, despite possessing the capacity to edit both enthalpic and entropic traps in the folding pathway of the substrate protein. © 2020 Elsevier Ltd
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Published in Academic Press
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