LAUSR

Calmodulin (CaM) binds to the membrane‐proximal cytosolic C‐terminal domain of CaV1.2 (residues 1520–1669, CT(1520–1669)) and causes Ca2+‐induced conformational changes that promote Ca2+‐dependent channel inactivation (CDI). We report biophysical studies that probe the structural interaction between CT(1520–1669) and CaM. The recombinantly expressed CT(1520–1669) is insoluble, but can be solubilized in the presence of Ca2+‐saturated CaM (Ca4/CaM), but not in the presence of Ca2+‐free CaM (apoCaM). We show that half‐calcified CaM (Ca2/CaM12) forms a complex with CT(1520–1669) that is less soluble than CT(1520–1669) bound to Ca4/CaM. The NMR spectrum of CT(1520–1669) reveals spectral differences caused by the binding of Ca2/CaM12 versus Ca4/CaM, suggesting that the binding of Ca2+ to the CaM N‐lobe may induce a conformational change in CT(1520–1669).