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Effects of macromolecular crowding on protein folding and aggregation
Author(s) -
van den Berg Bert,
Ellis R.John,
Dobson Christopher M.
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.24.6927
Subject(s) - biology , macromolecular crowding , protein folding , folding (dsp implementation) , crowding , protein aggregation , macromolecular substances , macromolecule , protein stability , computational biology , biophysics , biological system , biochemistry , neuroscience , electrical engineering , engineering
We have studied the effects of polysaccharide and protein crowding agents on the refolding of oxidized and reduced hen lysozyme in order to test the prediction that association constants of interacting macromolecules in living cells are greatly increased by macromolecular crowding relative to their values in dilute solutions. We demonstrate that whereas refolding of oxidized lysozyme is hardly affected by crowding, correct refolding of the reduced protein is essentially abolished due to aggregation at high concentrations of crowding agents. The results show that the protein folding catalyst protein disulfide isomerase is particularly effective in preventing lysozyme aggregation under crowded conditions, suggesting that crowding enhances its chaperone activity. Our findings suggest that the effects of macromolecular crowding could have major implications for our understanding of how protein folding occurs inside cells.