Kinetic partitioning during protein folding yields multiple native states.

The prevailing view in the field of protein folding holds that the native state is the most stable structure possible. A corollary of this thermodynamic hypothesis is that the native state is in equilibrium with all other conformations of the protein. We have found an example of a protein that may exist in two different states, both of which may be regarded as 'native', but which cannot equilibrate on a timescale that is biologically meaningful. We propose that the active conformation of this protein is at only one of several energy minima, and that during the process of refolding in vitro--and, we assume, folding in vivo--the choice of which state the polypeptide finally attains is determined by kinetic partitioning between folding pathways.