Energetics of angstrom-scale conformational changes in an RCK domain of the MthK K(+) channel

Allosteric proteins transition among different conformational states in a ligand-dependent manner. Upon resolution of a protein's individual states, one can determine the probabilities of these states, thereby dissecting the energetic mechanisms underlying their conformational changes. Here we examine individual RCK domains that form the regulatory module of the Ca(2+)-activated MthK channel. Each domain adopts multiple conformational states differing on an angstrom scale. The probabilities of these different states of the domain, assessed in different Ca(2+) concentrations, allowed us to fully determine a six-state model that is minimally required to account for the energetic characteristics of the Ca(2+)-dependent conformational changes of an RCK domain. From the energetics of this domain we deduced, in the framework of statistical mechanics, an analytic model that quantitatively predicts the experimentally observed Ca(2+) dependence of the channel's open probability.