Figure 1. Overall architecture of the ternary complexes containing a Na_V CTD, CaM, and a FHF.

(A) Sequence alignment of the Na_V1.2 and Na_V1.5 CTDs, with structural motifs and the IQ domain indicated. The interaction sites for the CaM N- and C-lobes and the CaM interlobular linker are also indicated. Human disease mutations in Na_V1.2 and Na_V1.5 clustering in the IQ domain are indicated in red; in blue are the homologous positions of disease mutations in Na_V1.1. (B) The Na_V1.2/Ca²⁺ structure containing the Na_V1.2 CTD (purple), FGF13 (silver), and CaM (blue). (C) The Na_V1.5/Ca²⁺ structure containing the Na_V1.5 CTD (orange), FGF12 (pink), and CaM (red). (D) Overlay of the Na_V1.2/Ca²⁺ and the Na_V1.5/Ca²⁺ structures aligned to the IQ motifs. (E) Overlay of the Na_V1.2/Ca²⁺ structure; the Na_V1.5/Ca²⁺ structure; and the Na_V1.5/-Ca²⁺ structure (Protein Data Bank accession code 4DCK), all aligned to the globular domain of the respective CTDs. For clarity, their respective CaM structures were omitted. This arrangement emphasizes the different angles between the globular domains and the IQ motifs among the three structures.