PMID:12947041
| Citation |
Takagi, F, Koga, N and Takada, S (2003) How protein thermodynamics and folding mechanisms are altered by the chaperonin cage: molecular simulations. Proc. Natl. Acad. Sci. U.S.A. 100:11367-72 |
|---|---|
| Abstract |
How the Escherichia coli GroEL/ES chaperonin assists folding of a substrate protein remains to be uncovered. Recently, it was suggested that confinement into the chaperonin cage itself can significantly accelerate folding of a substrate. Performing comprehensive molecular simulations of eight proteins confined into various sizes L of chaperonin-like cage, we explore how and to what extent protein thermodynamics and folding mechanisms are altered by the cage. We show that a substrate protein is remarkably stabilized by confinement; the estimated increase in denaturation temperature DeltaTf is as large as approximately 60 degrees C. For a protein of size R0, the stabilization DeltaTf scales as (R0/L)nu, where nu approximately 3, which is consistent with a mean field theory of polymer. We also found significant free energy cost of confining a protein, which increases with R0/L, indicating that the confinement requires external work provided by the chaperonin system. In kinetic study, we show the folding is accelerated in a modestly well confined case, which is consistent with a recent experimental result on ribulose-1,5-bisphosphate carboxylase-oxygenase folding and simulation results of a beta hairpin. Interestingly, the acceleration of folding is likely to be larger for a protein with more complex topology, as quantified by the contact order. We also show how ensemble of folding pathways are altered by the chaperonin-like cage calculating a variant of value used in the study of spontaneous folding. |
| Links |
PubMed PMC208763 Online version:10.1073/pnas.1831920100 |
| Keywords |
Chaperonins/chemistry; Kinetics; Protein Folding; Proteins/chemistry; Thermodynamics |
| edit table |
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