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Macromolecular crowding perturbs protein refolding kinetics: implications for folding inside the cell
Author(s) -
van den Berg Bert,
Wain Rachel,
Dobson Christopher M,
Ellis R John
Publication year - 2000
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/19.15.3870
Subject(s) - macromolecular crowding , biology , protein folding , kinetics , folding (dsp implementation) , biophysics , crowding , microbiology and biotechnology , macromolecule , protein stability , macromolecular substances , biochemistry , neuroscience , physics , engineering , quantum mechanics , electrical engineering
We have studied the effects of macromolecular crowding on protein folding kinetics by studying the oxidative refolding of hen lysozyme in the absence and presence of high concentrations of bovine serum albumin and Ficoll 70. The heterogeneity characteristic of the lysozyme refolding process is preserved under crowded conditions. This, together with the observation that the refolding intermediates that accumulate to significant levels are very similar in the absence and presence of Ficoll, suggests that crowding does not alter substantially the energetics of the protein folding reaction. However, the presence of high concentrations of macromolecules results in the acceleration of the fast track of the refolding process whereas the slow track is substantially retarded. The results can be explained by preferential excluded volume stabilization of compact states relative to more unfolded states, and suggest that, relative to dilute solutions, the rates of many protein folding processes are likely to be altered under conditions that more closely resemble the intracellular environment.