SPECIFIC INTERACTIONS BETWEEN THE SYNTROPHIN PDZ DOMAIN AND VOLTAGE-GATED SODIUM-CHANNELS

Syntrophins are modular proteins belonging to the dystrophin associate d glycoprotein complex and are thought to be involved in the regulatio n of the muscular system. Screening of peptide libraries revealed sele ctivity of the synotrophin PDZ domain toward the motif R/K/Q-E-S/T-X-V -COO- found to be highly conserved in the alpha-subunit C-terminus of vertebrate voltage gated sodium channels (VGSCs). The solution structu re of the domain in complex with the peptide G-V-K-E-S-L-V shows speci fic interactions between the conserved residues in the peptide and syn trophin-characteristic residues of the domain. We propose that syntrop hins localize VGSCs to the dystrophin network through its PDZ domain.