Structural influence of hanatoxin binding on the carboxyl terminus of S3 segment in voltage-gated K+-channel Kv2.1

The voltage-sensing domains of voltage-gated potassium channels Kv2.1 (drk1) contain four transmembrane segments in each subunit, termed S1 to S4. While S4 is known as the voltage sensor, the carboxyl terminus of S3 (S3(C)) bears a gradually broader interest concerning the site for gating modifier toxins like hanatoxin and thus the secondary structure arrangement as well as its surrounding environment. To further examine the putative three-dimensional (3-D) structure of S3(C) and to illustrate the residues required for hanatoxin binding (which may, in turn, show the influence on the S4 in terms of changes in channel gating), molecular simulations and dockings were performed. These were based on the solution structure of hanatoxin and the structural information from lysine-scanning results for S3(C) fragment. Our data suggest that several basic and acidic residues of hanatoxin are electrostatically and sterectchemically mapped onto their partner residues on S3(C) helix, whereas some aromatic or hydrophobic residues located on the same helical fragment interact with the hydrophobic patch of the toxin upon binding. Therefore, a slight distortion of the S3(C) helix, in a direction toward the N-terminus of S4, may exist. Such conformational change of S3(C) upon toxin binding is presented as a possible explanation for the observed shift in hanatoxin binding-induced gating.