title: Effects of macromolecular crowding on protein folding and aggregation.
abstract: 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.
authors.affiliation: Oxford Centre for Molecular Sciences, New Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QT.
authors.forename: B
authors.initials: B
authors.lastname: van den Berg
authors.forename: R J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: C M
authors.initials: CM
authors.lastname: Dobson
mesh_terms: D000818:Animals; D002645:Chickens; D005260:Female; D007700:Kinetics; D046911:Macromolecular Substances; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D011489:Protein Denaturation; D017510:Protein Folding; D020673:Protein Renaturation; D020836:Protein Structure, Quaternary; D014508:Urea
chemical_list: D046911:Macromolecular Substances; D014508:Urea; D009113:Muramidase