Protein chain collapse modulation and folding stimulation by GroEL-ES

Mohsin M. Naqvi, Mario J. Avellaneda, Andrew Roth, Eline J. Koers, Antoine Roland, Vanda Sunderlikova, Günter Kramer, Hays S. Rye, Sander J. Tans*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

The collapse of polypeptides is thought important to protein folding, aggregation, intrinsic disorder, and phase separation. However, whether polypeptide collapse is modulated in cells to control protein states is unclear. Here, using integrated protein manipulation and imaging, we show that the chaperonin GroEL-ES can accelerate the folding of proteins by strengthening their collapse. GroEL induces contractile forces in substrate chains, which draws them into the cavity and triggers a general compaction and discrete folding transitions, even for slow-folding proteins. This collapse enhancement is strongest in the nucleotide-bound states of GroEL and is aided by GroES binding to the cavity rim and by the amphiphilic C-terminal tails at the cavity bottom. Collapse modulation is distinct from other proposed GroEL-ES folding acceleration mechanisms, including steric confinement and misfold unfolding. Given the prevalence of collapse throughout the proteome, we conjecture that collapse modulation is more generally relevant within the protein quality control machinery.

Original languageEnglish
Article numbereabl6293
Number of pages10
JournalScience Advances
Volume8
Issue number9
DOIs
Publication statusPublished - 2022

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