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Voltage-dependent K(+) channels transfer the voltage sensor movement into gate opening or closure through an electromechanical coupling. To test functionally whether an interaction between the S4-S5 linker (L45) and the cytoplasmic end of S6 (S6(T)) constitutes this coupling, the L45 in hKv1.5 was replaced by corresponding hKv2.1 sequence. This exchange was not tolerated but could be rescued by also swapping S6(T). Exchanging both L45 and S6(T) transferred hKv2.1 kinetics to an hKv1.5 background while preserving the voltage dependence. A one-by-one residue substitution scan of L45 and S6(T) in hKv1.5 further shows that S6(T) needs to be alpha-helical and forms a "crevice" in which residues I422 and T426 of L45 reside. These residues transfer the mechanical energy onto the S6(T) crevice, whereas other residues in S6(T) and L45 that are not involved in the interaction maintain the correct structure of the coupling.

Original publication




Journal article


J Gen Physiol

Publication Date





667 - 680


Amino Acid Sequence, Amino Acid Substitution, Energy Transfer, Humans, Ion Channel Gating, Kinetics, Membrane Potentials, Mutagenesis, Site-Directed, Potassium Channels, Voltage-Gated, Protein Interaction Domains and Motifs, Protein Structure, Secondary, Structure-Activity Relationship