Protein chain collapse modulation and folding stimulation by GroEL-ES

Protein chain collapse modulation and folding stimulation by GroEL-ES

Naqvi, Mohsin M. (AMOLF)
Avellaneda, Mario J. (AMOLF)
Roth, Andrew (Texas A and M University)
Koers, Eline J. (AMOLF)
Roland, A.P.J. (AMOLF)
Sunderlikova, Vanda (AMOLF)
Kramer, Günter (German Cancer Research Center; University of Heidelberg)
Rye, Hays S. (Texas A and M University)
Tans, S.J. (TU Delft BN/Sander Tans Lab; Kavli institute of nanoscience Delft; AMOLF)

2022

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.

http://resolver.tudelft.nl/uuid:d016ff63-f49e-40cb-8677-41701f405fde

https://doi.org/10.1126/sciadv.abl6293

2375-2548

Science Advances, 8 (9)

Institutional Repository

journal article

© 2022 Mohsin M. Naqvi, Mario J. Avellaneda, Andrew Roth, Eline J. Koers, A.P.J. Roland, Vanda Sunderlikova, Günter Kramer, Hays S. Rye, S.J. Tans