The cold shock protein CspB from Bacillus subtilis is only marginally stable, but it folds extremely fast in a simple N ⇌ U two-state reaction. The corresponding cold shock proteins from the thermophile Bacillus caldolyticus and the hyperthermophile Thermotoga maritima show strongly increased conformational stabilities, but unchanged very fast two-state refolding kinetics. The absence of intermediates in the folding of B. subtilis CspB is thus not a corollary of its low stability. Rather, two-state folding and an unusually native-like activated state of folding seem to be inherent properties of these small all-β proteins. There is no link between stability and folding rate, and numerous sequence positions exist which can be varied to modulate the stability without affecting the rate and mechanism of folding.
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Perl, D., Welker, C., Schindler, T. et al. Conservation of rapid two-state folding in mesophilic, thermophilic and hyperthermophilic cold shock proteins. Nat Struct Mol Biol 5, 229–235 (1998) doi:10.1038/nsb0398-229
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