article published yes Mohsin M. Naqvi author Mario Avellaneda Sarrió author DC4BA84C-56E6-11EA-AD5D-348C3DDC885E0000-0001-6406-524X Andrew Roth author Eline J. Koers author Antoine Roland author Vanda Sunderlikova author Günter Kramer author Hays S. Rye author Sander J. Tans author MiSi department 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. https://research-explorer.ista.ac.at/download/17072/17357/2022_ScienceAdv_Naqvi.pdf application/pdfno American Association for the Advancement of Science2022 eng 2375-2548 3524511710.1126/sciadv.abl6293 89 Naqvi MM, Avellaneda Sarrió M, Roth A, et al. Protein chain collapse modulation and folding stimulation by GroEL-ES. <i>Science Advances</i>. 2022;8(9). doi:<a href="https://doi.org/10.1126/sciadv.abl6293">10.1126/sciadv.abl6293</a> Naqvi, M. M., Avellaneda Sarrió, M., Roth, A., Koers, E. J., Roland, A., Sunderlikova, V., … Tans, S. J. (2022). Protein chain collapse modulation and folding stimulation by GroEL-ES. <i>Science Advances</i>. American Association for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.abl6293">https://doi.org/10.1126/sciadv.abl6293</a> M. M. Naqvi <i>et al.</i>, “Protein chain collapse modulation and folding stimulation by GroEL-ES,” <i>Science Advances</i>, vol. 8, no. 9. American Association for the Advancement of Science, 2022. Naqvi, Mohsin M., et al. “Protein Chain Collapse Modulation and Folding Stimulation by GroEL-ES.” <i>Science Advances</i>, vol. 8, no. 9, eabl6293, American Association for the Advancement of Science, 2022, doi:<a href="https://doi.org/10.1126/sciadv.abl6293">10.1126/sciadv.abl6293</a>. Naqvi, Mohsin M., Mario Avellaneda Sarrió, Andrew Roth, Eline J. Koers, Antoine Roland, Vanda Sunderlikova, Günter Kramer, Hays S. Rye, and Sander J. Tans. “Protein Chain Collapse Modulation and Folding Stimulation by GroEL-ES.” <i>Science Advances</i>. American Association for the Advancement of Science, 2022. <a href="https://doi.org/10.1126/sciadv.abl6293">https://doi.org/10.1126/sciadv.abl6293</a>. M.M. Naqvi, M. Avellaneda Sarrió, A. Roth, E.J. Koers, A. Roland, V. Sunderlikova, G. Kramer, H.S. Rye, S.J. Tans, Science Advances 8 (2022). Naqvi MM, Avellaneda Sarrió M, Roth A, Koers EJ, Roland A, Sunderlikova V, Kramer G, Rye HS, Tans SJ. 2022. Protein chain collapse modulation and folding stimulation by GroEL-ES. Science Advances. 8(9), eabl6293. 170722024-05-29T06:12:19Z2024-08-05T08:30:29Z