Calmodulin: Definition, Structure, and Function

Calmodulin Definition

Calmodulin is a calcium-binding protein found in the cytoplasm of all eukaryotic cells. It is involved in regulating many biochemical and physiological processes, including muscle contraction. Calmodulin is expressed in all eukaryotic organisms and is considered a multifunctional intermediate calcium-binding messenger protein.

What is Calmodulin?

Calmodulin is a calcium-binding protein found in the cytoplasm of all eukaryotic cells. It is encoded by multiple genes, CALM1, CALM2, and CALM3, which are found on chromosomes 14, 2, and 19 respectively in humans.

Calmodulin forms two globular domains connected by a flexible central linker. Each domain binds two calcium ions. When Ca2+ binds to calmodulin it forms the Ca2+/calmodulin complex which then interacts with other proteins in the cell.

These proteins are enzymes and effector proteins involved in a variety of cellular and physiological processes.

Calmodulin plays an important role in many calcium-mediated processes such as nerve impulse transmissions and muscle action. It also plays an important role in lipid metabolism by affecting Calcitonin.

Calcitonin is a polypeptide hormone that lowers blood Ca2+ levels and activates G protein cascades that lead to the generation of cAMP. The actions of calcitonin can be blocked by inhibiting the actions of calmodulin suggesting that calmodulin plays a crucial role in the activation of calcitonin.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a crucial role in long-term potentiation (LTP), which requires the presence of calcium/calmodulin. LTP is a type of synaptic plasticity that contributes to short-term and long-term memory.

In Arabidopsis thaliana study, hundreds of different proteins were identified as potential targets for calmodulin regulation.

Calmodulin Structure

Calmodulin is a small, highly conserved protein that is 148 amino acids long and has two approximately symmetrical globular domains connected by a flexible linker. Each end of calmodulin binds to two calcium ions through helix-loop-helix domains similar to those found in other calcium-binding proteins.

The C-domain has a higher binding affinity for Ca2+ than the N-domain. Calmodulin remains a dumb-bell-shaped molecule, with similar lobes and connected by a central alpha-helix.

Each lobe contains three alpha-helices and two Ca2+ binding EF hand loops, with a short antiparallel beta-sheet between adjacent EF hand loops and one non-EF hand loop.

Calmodulin acts as an intermediary protein that senses calcium levels and relays signals to various calcium-sensitive enzymes, ion channels, and other proteins.

It plays an important role in the activation of phosphorylase kinase, which ultimately leads to glucose being cleaved from glycogen-by-glycogen phosphorylase.

Calmodulin also plays an important role in lipid metabolism by affecting Calcitonin. Calcitonin is a polypeptide hormone that lowers blood Ca2+ levels and activates G protein cascades that lead to the generation of cAMP. The actions of calcitonin can be blocked by inhibiting the actions of calmodulin.

The crystal structure of calmodulin shows it without calcium as well as after calcium binds. When calcium binds, non-polar amino acids form two neat grooves waiting to grip the target protein.

Because these non-polar grooves are generic in shape, calmodulin acts as a versatile regulatory protein and its targets are not required to possess any specific amino acid sequence or structural binding motifs.

Calmodulin Function

Calmodulin is a calcium-modulated protein that binds calcium ions as they enter the intracellular space. It is present in all eukaryotic cells and serves as the primary intracellular receptor for Ca2+.

Calmodulin acts as an intermediary protein that senses calcium levels and relays signals to various calcium-sensitive enzymes, ion channels, and other proteins.

It plays an important role in the activation of phosphorylase kinase, which ultimately leads to glucose being cleaved from glycogen-by-glycogen phosphorylase. Calmodulin also plays an important role in lipid metabolism by affecting Calcitonin.

Calcitonin is a polypeptide hormone that lowers blood Ca2+ levels and activates G protein cascades that lead to the generation of cAMP.

Calmodulin is a small dumbbell-shaped protein composed of two globular domains connected together by a flexible linker. Each end binds to two calcium ions. As its name suggests, calmodulin is a Calcium Modulated protein.

It is abundant in the cytoplasm of all higher cells and has been highly conserved through evolution. Because its non-polar grooves are generic in shape, calmodulin acts as a versatile regulatory protein, and its targets are not required to possess any specific amino acid sequence or structural binding motifs.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a crucial role in long-term potentiation (LTP), which requires the presence of calcium/calmodulin. LTP is a type of synaptic plasticity known to contribute to short-term and long-term memory formation.

Calcium          

Calmodulin is a calcium-modulated protein that plays an essential role in calcium-dependent signaling. It acts as an intermediary protein that senses calcium levels and relays signals to various calcium-sensitive enzymes, ion channels, and other proteins.

Calmodulin binds to calcium ions during the induction of intracellular signaling. The coordination geometry of calmodulin’s binding site is heptadentate because the calcium ion interacts with seven donor atoms.

Calmodulin has two non-polar grooves that grip the target protein when calcium binds, making it a versatile regulatory protein whose targets are not required to possess any specific amino acid sequence or structural binding motifs.

Calcium participates in an intracellular signaling system by acting as a diffusible second messenger to the initial stimuli. It does this by binding various targets in the cell, including a large number of enzymes, ion channels, aquaporins, and other proteins.

Calcium/calmodulin-dependent protein kinases (CaMKs) are key regulators of calcium signaling in health and disease. CaMKII plays a crucial role in a type of synaptic plasticity known as long-term potentiation (LTP), which requires the presence of calcium/calmodulin.

CaMKII contributes to the phosphorylation of an AMPA receptor which increases the sensitivity of AMPA.

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