Fig. 4.
The S3–S4 loop of hHv1 is the binding epitope for C6. hHv1, CiHv1, and chimera channels were expressed in HEK293T cells and studied as described in Fig. 3. (A) Sequence alignments of the S3–S4 motif of hHv1 (black), CiHv1 (blue), and loop transplanting chimeras. The S3–S4 loop of hHv1 or CiHv1 were transplanted into the corresponding region of CiHv1 or hHv1 to produce functional chimeric channels, hS3-S4CiHv1 and CiS3-S4hHv1, respectively. (B) Representative proton current trace for channels (black trace) in the absence or presence of 1 µM C6 (red trace, inhibition at +40 mV after toxin wash-in as indicated by red arrows). Left, CiHv1; Center, CiS3-S4hHv1; Right, hS3-S4CiHv1. The S3–S4 loop of hHv1 can be transplanted to CiHv1 to confer toxin sensitivity in hS3-S4CiHv1 chimeric channel.