Calcium-binding proteins are proteins that participate in calcium cell signalling

pathways by binding to Ca2+.

The most ubiquitous Ca2+-sensing protein, found in all eukaryotic organisms including
yeasts, is calmodulin.
Intracellular storage and release of Ca2+ from the sarcoplasmic reticulum is
associated with the high-capacity, low-affinity calcium-binding protein calsequestrin.
With their role in signal transduction, calcium-binding proteins contribute to all
aspects of the cell's functioning, from homeostasis to learning and memory.
For example, the neuron-specific calexcitin has been found to have an excitatory
effect on neurons, and interacts with proteins that control the firing state of
neurons, such as the voltage-dependent potassium channel

Calmodulin
Function
CaM mediates processes such as inflammation, metabolism, apoptosis, smooth muscle
contraction, intracellular movement, short-term and long-term memory, nerve growth
and the immune response. CaM is expressed in many cell types and can have different
subcellular locations, including the cytoplasm, within organelles, or associated with the
plasma or organelle membranes. Many of the proteins that CaM binds are unable to
bind calcium themselves, and as such use CaM as a calcium sensor and signal
transducer. CaM can also make use of the calcium stores in the endoplasmic reticulum,
and the sarcoplasmic reticulum. CaM undergoes a conformational change upon binding
to calcium, which enables it to bind to specific proteins for a specific response. CaM
can bind up to four calcium ions, and can undergo post-translational modifications,
such as phosphorylation, acetylation, methylation and proteolytic cleavage, each of
which has potential to modulate its actions. Calmodulin can also bind to edema factor
toxin from the anthrax bacteria.
Structure

Calmodulin is a small, acidic protein approximately 148 amino acids long (16706 Dalton)
and, as such, is a favorite for testing protein simulation software. It contains four
EF-hand "motifs", each of which binds a Ca2+ ion. The protein has two approximately
symmetrical domains, separated by a flexible "hinge" region. Calcium participates in an
intracellular signalling system by acting as a diffusible second messenger to the initial
stimuli.
Mechanism
Calcium is bound via the use of the EF hand motif, which supplies an electronegative
environment for ion coordination. After calcium binding, hydrophobic methyl groups
from methionine residues become exposed on the protein via conformational change.
This presents hydrophobic surfaces, which can in turn bind to Basic Amphiphilic
Helices (BAA helices) on the target protein. These helices contain complementary
hydrophobic regions. The flexibility of Calmodulin's hinged region allows the molecule
to "wrap around" its target. This property allows it to tightly bind to a wide range of
different target proteins.

Calsequestrin
Calsequestrin is a calcium-binding protein of the sarcoplasmic reticulum. The protein
helps hold calcium in the cisterna of the sarcoplasmic reticulum after a muscle
contraction, even though the concentration of calcium in the sarcoplasmic reticulum is
much higher than in the cytosol. It also helps the sarcoplasmic reticulum store an
extraordinarily high amount of calcium ions. Each molecule of calsequestrin can bind
18 to 50 Ca2+ ions. [1] Sequence analysis has
suggested that calcium is not bound in
distinct pockets via EF-hand motifs, but
via

presentation

of

charged

rather

protein

surface. Two forms of calsequestrin have

been

identified. The cardiac form (Calsequestrin2/CASQ2) is present in cardiac and slow

skeletal muscle and the fast skeletal form
(Calsequestrin-1/CASQ1) is found in fast
skeletal

muscle.

The

release

of

calsequestrin-bound calcium (through a a calcium release channel) triggers muscle

contraction. The active protein is not highly structured, more than 50% of it adopting
a random coil conformation.[2] When calcium binds there is a structural change
whereby the alpha-helical content of the protein increases from 3 to 11%.[2] Both

forms of calsequestrin are phosphorylated by casein kinase II, but the cardiac form
is phosphorylated more rapidly and to a higher degree