Folding of Ubiquitin: A Simple Model Describes the Strange Kinetics

The ubiquitin mutant Ub*G folding expts. of Sabelko et al. (Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 6031-​6036)​, in which "strange kinetics" were obsd., 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-​temp. expts. of Sabelko et al. Are fitted by a system of kinetic equations detg. the transitions between these states. It is possible that cold- and heat-​denaturated states of Ub*G are the basis of the off-​pathway traps. The fits of the kinetic model to the exptl. results provides an est. of the rate consts. for the various reaction channels and show how their contributions vary with temp. Introduction of an on-​pathway intermediate instead of one of the off-​pathway traps does not lead to agreement with the expts.