The lipid-protein interface of a Shaker K+ channel

Tryptophan-substitution mutagenesis was applied to the first and third tran smembrane segments (S1 and S3) of a Shaker-type K+ channel for the purpose of ascertaining whether these sequences are alpha-helical. Point mutants we re examined for significant functional changes, indicated by the voltage-ac tivation curves and gating kinetics, Helical periodicity of functional alte ration was observed throughout the entire S1 segment. A similar result was obtained with the first 14 residues of S3, but this periodicity disappeared to towards the extracellular side of this transmembrane sequence. In both helical stretches, tryptophan-tolerant positions are clustered on approxima tely half die alpha-helix surface, as if the sidechains are exposed to the hydrocarbon region of the lipid bilayer: These results, combined with an an alogous study of S2 (Monks, S., D.J. Needleman, and C, Miller 1999. J. Gen. Physiol. 113:415-423), locate S1, S2, and S3 on the lipid-facing periphery of K-v channels.