Potassium channel folding assessed by hydrogen exchange mass spectrometry and tryptophan fluorescence identifies pore helix and selectivity filter folding events

Abstract

While the function of ion channels is critical for numerous physiological processes, how they achieve their three-dimensional fold and assemble remains an open topic. Outstanding questions concern the identification of the rate-limiting step, when the selectivity filter folds, and the role of a protein-dense phase in folding. We have made significant progress in characterizing the in vitro folding of the KcsA transmembrane pore domain, a robust model system for the pore domain of human potassium channels such as hERG and Kv1.2.