Electrostatic interaction between dipoles and side chains in the voltage sensor domain of K(+) channel.

Background: It is well known that α-helices of protein, possessing equal and opposite charged ends, behaves like a macrodipole, but the relative importance of such macrodipoles to the aggregation of a pair of helix in the voltage sensor domain (VSD) of K+ ion channel, has not been assessed. In the VSD, importance has been given primarily to the helically arranged Arginine residues of helix, but the role of the charged residues of S3b is less focused.

Method And Objective: Applying electrostatic theory, we have studied the interaction between the charges of S3b-S4 α-helix pair of KvAP through virtual mutagenesis.

Result And Conclusion: We have shown that the terminal charges arising from the inherent dipolar property of α-helices play an important role in affecting the stability of the S3b-S4 pair, and in determining its spatial position at zero transmembrane potential. Moreover, the negatively charged side chain of S3b was found to be the primary stabilizing factor in holding S3b-S4 pair together as a "paddle". Comparison of sequences of S3b helix of K+ channels from different species showed a previously unreported positional conservation of negative residues, highlighting their functional importance. These charges may contribute to the energetic of α-helix movements in an electric field.