Effects of macromolecular crowding on protein folding and aggregation

被引:420
作者
van den Berg, B
Ellis, RJ
Dobson, CM
机构
[1] Univ Oxford, Oxford Ctr Mol Sci, New Chem Lab, Oxford OX1 3QT, England
[2] Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England
基金
英国惠康基金;
关键词
chaperone; hen lysozyme; macromolecular crowding; protein disulfide isomerase; protein folding;
D O I
10.1093/emboj/18.24.6927
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:6927 / 6933
页数:7
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