Related Experiment Video
Updated: Aug 10, 2026

4D Imaging of Protein Aggregation in Live Cells
Published on: April 5, 2013
Protein folding stability can determine the efficiency of escape from endoplasmic reticulum quality control
J M Kowalski1, R N Parekh, J Mao
1Department of Chemical Engineering, University of Illinois, Urbana, Illinois 61801, USA.
Abstract:
A fraction of each secreted protein is retained and degraded by the endoplasmic reticulum (ER) quality control apparatus that restricts export to correctly folded proteins. The intrinsic biophysical attributes that determine efficiency of escape from this proofreading process have been examined by expressing mutants of bovine pancreatic trypsin inhibitor (BPTI) in yeast. Secretion efficiency is strongly correlated with thermodynamic stability for a series of six point mutations of BPTI. No correlation of secretion efficiency with either oxidative folding or refolding rates in vitro is found; both the rapidly folded Y35L BPTI mutant and the slowly unfolded G36D BPTI mutant exhibit low secretion efficiency. Elimination of cysteines 14 and 38 by mutagenesis does not increase secretion efficiency, indicating that intramolecular thiol/disulfide rearrangements are not primarily responsible for retention and degradation of destabilized BPTI variants. Mutant yeast strains with diminished ER-associated degradation do not secrete BPTI more efficiently, indicating that retention and degradation are separable processes. These data support a model for ER quality control, wherein protein folding is functionally reversible and the relative rates of folding, unfolding, vesicular export, and retention determine secretion efficiency.
Related Concept Videos
Molecular Chaperones and Protein Folding
The...
Protein Folding Quality Check in the RER
The Unfolded Protein Response
Export of Misfolded Proteins out of the ER
Protein Folding
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Molecular Chaperones and Protein Folding
The...

