Calmodulin-binding proteins are, as their name implies, proteins which bind calmodulin. Calmodulin can bind to a variety of proteins through a two-step binding mechanism, namely "conformational and mutually induced fit", where typically two domains of calmodulin wrap around an emerging helical calmodulin binding domain from the target protein. Examples include: Gap-43 protein (presynaptic) Neurogranin (postsynaptic) Caldesmon Ca2+ Activation A variety of different ions, including Calcium (Ca2+), play a vital role in the regulation of cellular functions. Calmodulin, a Calcium-binding protein, that mediates Ca2+ signaling is involved in all types of cellular mechanisms, including metabolism, synaptic plasticity, nerve growth, smooth muscle contraction, etc. Calmodulin allows for a number of proteins to aid in the progression of these pathways using their interactions with CaM in its Ca2+-free or Ca2+-bound state. Proteins each have their own unique affinities for calmodulin, that can be manipulated by Ca2+ concentrations to allow for the desired release or binding to calmodulin that determines its ability to carry out its cellular function. Proteins that get activated upon binding to Ca2+-bound state, include Myosin light-chain kinase, Phosphatase, Ca2+/calmodulin-dependent protein kinase II, etc. Proteins, such as neurogranin that plays a vital role in postsynaptic function, however, can bind to calmodulin in Ca2+-free or Ca2+-bound state via their IQ calmodulin-binding motifs. Since these interactions are exceptionally specific, they can be regulated through post-translational modifications by enzymes like kinases and phosphatases to affect their cellular functions. In the case of neurogranin, it's the synaptic function can be inhibited by the PKC-mediated phosphorylation of its IQ calmodulin-binding motif that impedes its interaction with calmodulin. Cellular functions can be indirectly regulated by calmodulin, as it acts as a mediator for enzymes that require Ca2+ stimulation for activation. Studies have proven that calmodulin's affinity for Ca2+ increases when it is bound to a calmodulin-binding protein, which allows for it to take on its regulatory role for Ca2+-dependent reactions. Calmodulin, made up of two pairs of EF-hand motifs separated in different structural regions by an extended alpha helical region, that permits it to respond to the changes in the cytosolic concentration of the Ca2+ ions by taking on two distinct conformations, in the inactive Ca2+ unbound state and active Ca2+ bound state. Calmodulin binds to the targeted proteins via their short complementary peptide sequences, causing an “induced fit” conformational change that alters the calmodulin-binding proteins’ activity as desired in response to the second messenger Ca2+ signals