POLARITY-DEPENDENT CONFORMATIONAL SWITCHING OF A PEPTIDE MIMICKING THE S4-S5 LINKER OF THE VOLTAGE-SENSITIVE SODIUM-CHANNEL

The S4-S5 linker (or 545) in voltage-sensitive sodium channels was pre viously shown to be involved in the permeation pathway. The secondary structure, investigated by circular dichroism, of a S4-S45 peptide fro m domain IV and its fragments (including S45) is reported here and com pared with that of the homologous peptide from domain II as a function of the solvent dielectric constant. The reduction in helicity seen fo r S4-S45 (II) in polar media is cancelled in membrane-like environment . The most striking result - a sharp alpha-helix --> beta-sheet transi tion upon exposure of the S45 moiety to aqueous solvents - is discusse d as regards channel activation and selectivity.