Folding of ubiquitin: a simple model describes the strange kinetics

The ubiquitin mutant UbG folding experiments of Sabelko et al., in which "strange kinetics" were observed, are interpreted in terms of a simple kinetic model. A minimal set of states consisting of a semicompact globule, two off-pathway traps, and the native state are included; the fully unfolded state is not considered because folding to the semicompact globule is fast. Both the low- and the high-temperature experiments of Sabelko et al. are fitted by a system of kinetic equations determining the transitions between these states. It is possible that cold- and heat-denaturated states of UbG are the basis of the off-pathway traps. The fits of the kinetic model to the experimental results provides an estimate of the rate constants for the various reaction channels and show how their contributions vary with temperature. Introduction of an on-pathway intermediate instead of one of the off-pathway traps does not lead to agreement with the experiments.