calcitonin gene-related peptide binding

Definition

Target type: molecularfunction

Binding to calcitonin gene-related peptide (CGRP). [GOC:bhm, PMID:10882736]

Calcitonin gene-related peptide (CGRP) binding involves the interaction of CGRP with its cognate receptor, the CGRP receptor (CGRP-R), which is a heterodimer composed of the calcitonin receptor-like receptor (CLR) and the receptor activity modifying protein 1 (RAMP1). The binding of CGRP to CGRP-R triggers a series of intracellular signaling events that ultimately lead to the activation of downstream effectors. The molecular function of CGRP binding can be described in detail as follows:

1. **Ligand Recognition:** CGRP, a 37-amino acid peptide, binds to the extracellular domain of the CLR subunit of the CGRP-R. The binding is highly specific, with CGRP showing a much higher affinity for CGRP-R than for other receptors, such as the calcitonin receptor.

2. **Receptor Activation:** Upon CGRP binding, the CLR subunit undergoes a conformational change, which activates the receptor complex. This activation involves the recruitment of G proteins, specifically Gαs, to the intracellular domain of the CLR subunit.

3. **Signal Transduction:** The activated Gαs protein dissociates from the receptor and activates adenylyl cyclase, an enzyme responsible for converting ATP into cyclic adenosine monophosphate (cAMP). cAMP acts as a second messenger, triggering a cascade of downstream signaling events.

4. **Activation of Downstream Effectors:** Increased cAMP levels activate protein kinase A (PKA), which phosphorylates various intracellular proteins involved in cellular processes, including gene expression, cellular differentiation, and proliferation.

5. **Biological Effects:** CGRP binding and subsequent signal transduction mediate a wide range of biological effects, including:
- Vasodilation: CGRP promotes the relaxation of vascular smooth muscle, leading to vasodilation and increased blood flow.
- Neuroprotection: CGRP has neuroprotective effects, reducing neuronal damage in various neurological conditions.
- Pain Modulation: CGRP plays a role in pain perception and transmission, contributing to both acute and chronic pain.
- Inflammation: CGRP is involved in the inflammatory response, contributing to the recruitment of immune cells to the site of injury.

6. **Therapeutic Implications:** The involvement of CGRP in various physiological and pathological processes has led to the development of CGRP-targeted therapies, such as monoclonal antibodies and small-molecule inhibitors, for the treatment of migraines, cluster headaches, and other conditions associated with CGRP dysregulation.'
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Proteins (1)

Compounds (4)