calcitonin binding

Definition

Target type: molecularfunction

Binding to calcitonin, a peptide hormone responsible for reducing serum calcium levels by inhibiting osteoclastic bone reabsorption and promoting renal calcium excretion. It is synthesized and released by the C cells of the thyroid. [GOC:ecd]

Calcitonin binding is a complex process involving the interaction of calcitonin, a peptide hormone produced by the thyroid gland, with its cognate receptor, the calcitonin receptor (CTR). This receptor, a member of the G protein-coupled receptor (GPCR) family, is expressed primarily on osteoclasts, the cells responsible for bone resorption, and to a lesser extent on other cells, including chondrocytes, renal cells, and certain neurons.

Calcitonin binding to the CTR initiates a cascade of events that ultimately lead to a decrease in osteoclast activity and bone resorption. The binding process involves the following key steps:

1. **Initial Binding:** Calcitonin, a 32-amino acid peptide, binds to the extracellular domain of the CTR, which is composed of seven transmembrane domains. This binding is highly specific, relying on interactions between specific amino acid residues in calcitonin and the receptor.

2. **Conformational Change:** Upon binding, the CTR undergoes a conformational change, which activates the intracellular signaling pathways.

3. **G Protein Coupling:** The activated receptor interacts with a G protein, specifically a Gαs protein, located on the intracellular side of the membrane.

4. **Adenylyl Cyclase Activation:** The Gαs protein activates adenylyl cyclase, an enzyme that catalyzes the conversion of ATP to cyclic AMP (cAMP).

5. **cAMP Signaling:** cAMP acts as a second messenger, activating protein kinase A (PKA), a downstream effector.

6. **Downstream Targets:** PKA phosphorylates various target proteins, leading to a cascade of events that ultimately reduce osteoclast activity. These targets include proteins involved in:
* Osteoclast differentiation and maturation
* Osteoclast adhesion to bone
* Osteoclast cytoskeletal organization
* Osteoclast acidification and enzyme secretion

The net effect of calcitonin binding to the CTR is a reduction in bone resorption, which contributes to maintaining calcium homeostasis in the body. Calcitonin is used clinically to treat certain bone diseases, such as Paget's disease, and hypercalcemia. Understanding the molecular function of calcitonin binding is crucial for developing new therapies targeting bone metabolism and other physiological processes regulated by the calcitonin receptor.'
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Proteins (2)

Compounds (2)