STRUCTURAL STUDIES OF SYNTHETIC PEPTIDES DISSECTED FROM THE VOLTAGE-GATED SODIUM-CHANNEL

Peptides representing transmembrane regions of the alpha-subunit of th e voltage-gated sodium channel were synthesised and their structures a nalysed, using H-1 NMR and CD, in trifluoroethanol and in dodecylphosp hocholine micelles. Sequence analysis suggests that the channel has si x regions, S1 to S6, predicted to span the membrane in four homologous domains, designated, I, II, III and IV. Presented here are studies of representatives examples of possible single spanning segments (IS2, I S4, IVS4) and a double spanning segment, IS34, composed of segments IS 3 and IS4. In addition, we investigated ISlink56, the putative Linker region between segments IS5 and IS6. All of the peptides were found to have predominantly alpha-helical structures in both solvent systems. There was some evidence for bending of the longer helices but there wa s no discernible evidence for well-defined tertiary structure. (C) 199 6 Academic Press Limited