CaM C-lobe conformations bound to Nav C-termini. The structures display a semi-open, not the open conformation typical of Ca-CaM. In the figure the colors are CaM C-lobe (yellow, PDB ID 2KXW), CTNav1.5-CaM (marine, PDB ID 40VN), CTNav1.5-CaM-FHF (navy blue, PDB ID 4DCK), CTNav1.2-CaM-Ca-FHF (teal, PDBID 4JPZ), IQNav1.2-apoCaM-(yellow, PDBID 2KXW), and CaM-Ca (Magenta, PDB ID 1CDM). (A) Overlap of the semi-open CaM C-lobe (PDB ID 2KXW) as seen IQNav1.2-CaM with CTNav1.5-CaM-FHF (PDB ID 4DCK). (B) 90° rotation from A. (C) Overlap of CaM C-lobe as seen in CaM-Ca (PDB ID 1CDM) with CTNav1.5-CaM-FHF (PDB ID 4DCK). (D) 90° rotation from (C). (E-G) and (K–M). CaM C-lobe displaying the lack of change in conformation of the helices upon Ca2+ binding with respect to semi open CaM C-lobe (rmsd for all pairwise aligments is ˜1.0 Å). (E, K)Alignment of the CTNav1.5-CaM C-lobe (4OVN) with CaM C-lobe (2KXW, rmsd 1.3 Å). (H, N) Alignment of the CTNav1.5-CaM C-lobe with CaM-Ca C-lobe (1CDM, rmsd 3.1 Å). (F, L) Alignment of the CTNav1.5-CaM-Ca-FHF C-lobe with CaM C-lobe (2KXW, rmsd 1.3 Å). (I, O) Alignment of the the CTNav1.5-CaCaM-FHF C-lobe with CaM-Ca C-lobe (rmsd 3.1 Å). (G, M) Alignment of the CTNav1.2-CaM-Ca-FHF C-lobe with CaM C-lobe (2KWC, rmsd 1.0 Å). (J, P) CTNav1.2-CaM-Ca-FHF C-lobe with CaMCa C-lobe (1CDM, rmsd 3.1 Å).