| Autor: |
Naqvi MM; AMOLF, Science Park 104, 1098 XG Amsterdam, Netherlands., Avellaneda MJ; AMOLF, Science Park 104, 1098 XG Amsterdam, Netherlands., Roth A; Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77845, USA., Koers EJ; AMOLF, Science Park 104, 1098 XG Amsterdam, Netherlands., Roland A; AMOLF, Science Park 104, 1098 XG Amsterdam, Netherlands., Sunderlikova V; AMOLF, Science Park 104, 1098 XG Amsterdam, Netherlands., Kramer G; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, Heidelberg D-69120, Germany.; German Cancer Research Center (DKFZ), Im Neuenheimer Feld 282, Heidelberg D-69120, Germany., Rye HS; Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77845, USA., Tans SJ; AMOLF, Science Park 104, 1098 XG Amsterdam, Netherlands.; Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, Netherlands. |
| Abstrakt: |
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. |
