The human ether-à-go-go related gene (hERG) encodes a protein that forms a voltage-gated potassium channel and plays an important role in the heart by controlling the rapid delayed rectifier K+ current (IKr). The S4–S5 linker was shown to be important for the gating of the hERG channel. Nuclear magnetic resonance study showed that a peptide derived from the S4–S5 linker had no well-ordered structure in aqueous solution and adopted a 310-helix (E544-Y545-G546) structure in detergent micelles. The existence of an amphipathic helix was confirmed, which may be important for interaction with cell membrane. Close contact between side chains of residues R541 and E544 was observed, which may be important for its regulation of channel gating. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.