Na1.2 EFL domain allosterically enhances Ca binding to sites I and II of WT and pathogenic calmodulin mutants bound to the channel CTD.

Neuronal voltage-gated sodium channel Na1.2 C-terminal domain (CTD) binds calmodulin (CaM) constitutively at its IQ motif. A solution structure (6BUT) and other NMR evidence showed that the CaM N domain (CaM) is structurally independent of the C-domain (CaM) whether CaM is bound to the Na1.