Figure 5.

Schematic of Ca²⁺/CaM lobe multiple binding modes on the Ca_V1.2 IQ domain. (a) Ca²⁺/N lobe (green) has medium-affinity and low-affinity binding sites on the IQ domain. (b) Ca²⁺/C lobe (blue) has a high-affinity binding site on the IQ domain. (c) Binding of Ca²⁺/C lobe to the IQ domain blocks Ca²⁺/N lobe access to the Ca²⁺/N lobe medium-affinity site (black X) and reduces Ca²⁺/N lobe binding to the Ca²⁺/N lobe low-affinity site (grey X). (d) Representation of how Ca²⁺/C lobe binding to the IQ domain tethers Ca²⁺/N lobe near the Ca²⁺/N lobe low-affinity site. Yellow line indicates the CaM interlobe linker. In all panels, the approximate position of aromatic anchor Phe1628, which is shared by the Ca²⁺/N lobe medium-affinity site and the Ca²⁺/C lobe high-affinity site, is indicated by the white hexagon.