Insights into modulation of calcium signaling by magnesium in calmodulin, troponin C and related EF-hand proteins

► “EF-hand” proteins convey intracellular Ca2+ signals in the presence of ~1000-fold excess of Mg2+. ► Due to stereochemical constraints Mg2+ ion cannot engage the ligands of an EF-hand in the same way as Ca2+. ► Mg2+ plays an active role in the Ca2+-dependent regulation of cellular processes by stabilizing the “off state” of some EF-hand proteins. ► Some pathological conditions attributed to Mg2+ deficiency might be related to excessive activation of underlying Ca2+-regulated cellular processes.