Ca2calmoduline

Ca2+-calmodulin (Ca2+-CaM) refers to the calcium-bound form of calmodulin, a ubiquitously expressed intracellular calcium-binding messenger protein found in all eukaryotes. It functions as a versatile signal transducer that translates changes in intracellular Ca2+ concentration into modulation of a broad range of target proteins and enzymes.

Calmodulin is a small acidic protein of about 17 kilodaltons, consisting of 148 amino acids arranged in two globular domains (N- and C-lobes) connected by a flexible central linker. Each domain contains two EF-hand motifs that coordinate Ca2+ ions. In the absence of Ca2+, calmodulin adopts a closed conformation; binding of Ca2+ induces a conformational change that reveals hydrophobic surfaces capable of interacting with target peptides, enabling regulation of their activity.

When bound to Ca2+, calmodulin modulates a variety of enzymes and channels, such as myosin light-chain kinase (MLCK), phosphorylase kinase, Ca2+/calmodulin-dependent protein kinases (CaMKs), and calcineurin. It also regulates adenylyl cyclases and various ion channels. The Ca2+-calmodulin complex acts as a calcium sensor and amplifier for signaling cascades, often via transient local Ca2+ microdomains.

Calmodulin is encoded by three highly conserved genes in humans (CALM1, CALM2, CALM3); their encoded proteins are identical in sequence and function. The Ca2+-calmodulin complex is short-lived and acts in a rapid, reversible manner to control diverse processes including muscle contraction, metabolism, gene expression, and synaptic plasticity.