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A putative interaction pair involving a residue in the S4-S5 linker and the end of S6 segment identified in a scanning mutagenesis study. Thermodynamic analysis of cooperative systems reveals that these sites are likely to interact both in the resting and activated state-acting as a spring to couple the sensor and effector domains. Although the overall architecture of the members of voltage-dependent ion channel superfamily is likely to be similar, the voltage-sensing domains of the sodium channels, unli.