Folding and misfolding of potassium channel monomers during assembly and tetramerization.

ABSTRACT: The dynamics and folding of potassium channel pore domain monomers are connected to the kinetics of tetramer assembly. In all-atom molecular dynamics simulations of Kv1.2 and KcsA channels, monomers adopt multiple nonnative conformations while the three helices remain folded. Consistent with this picture, NMR studies also find the monomers to be dynamic and structurally heterogeneous. However, a KcsA construct with a disulfide bridge engineered between the two transmembrane helices has an NMR spectrum with well-dispersed peaks, suggesting that the monomer can be locked into a native-like conformation that is similar to that observed in the folded tetramer. During tetramerization, fluoresence resonance energy transfer (FRET) data indicate that monomers rapidly oligomerize upon insertion int

SUBMITTER: Song KC 

PROVIDER: S-EPMC8403937 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature