CXCR chemokine receptor binding

Definition

Target type: molecularfunction

Binding to a chemokine receptor in the CXCR family. [GOC:ceb, PMID:11910892]

CXCR chemokine receptors are a family of G protein-coupled receptors (GPCRs) that play crucial roles in immune cell trafficking, inflammation, and development. These receptors bind to chemokines, small secreted proteins that act as chemoattractants and signaling molecules, initiating a cascade of intracellular events that regulate cell migration, activation, and differentiation. The molecular function of CXCR chemokine receptor binding involves a complex interplay of protein-protein interactions and signal transduction pathways.

1. **Chemokine Binding:** CXCR receptors possess a characteristic seven-transmembrane domain structure, with an extracellular N-terminus and an intracellular C-terminus. The binding site for chemokines resides within the extracellular domain, specifically within the N-terminus and the first extracellular loop. Chemokine binding to the receptor is highly specific and mediated by electrostatic interactions, hydrogen bonds, and hydrophobic interactions.

2. **Conformational Change:** Upon chemokine binding, the receptor undergoes a conformational change, altering its structure and activating the intracellular signaling cascade. This conformational change involves a shift in the transmembrane helices and the repositioning of key amino acid residues within the receptor.

3. **G Protein Coupling:** The activated CXCR receptor interacts with heterotrimeric G proteins, specifically Gαi proteins. This interaction triggers the dissociation of the Gαi subunit from the Gβγ dimer, releasing both subunits to initiate downstream signaling events.

4. **Signal Transduction:** The activated Gαi subunit inhibits adenylyl cyclase activity, leading to a decrease in cAMP levels. Simultaneously, the released Gβγ dimer activates other effector molecules, including phospholipase Cβ (PLCβ) and PI3 kinase.

5. **Cellular Responses:** The downstream signaling pathways activated by CXCR chemokine receptor binding lead to a variety of cellular responses, including:
* **Chemotaxis:** Directed migration of cells towards the chemokine gradient.
* **Cell Activation:** Induction of intracellular signaling pathways, leading to changes in gene expression, cytokine production, and cell survival.
* **Inflammation:** Recruitment of immune cells to sites of inflammation.
* **Development:** Regulation of hematopoietic cell development and differentiation.

The molecular function of CXCR chemokine receptor binding is essential for regulating immune cell behavior and orchestrating immune responses. Disruptions in CXCR signaling pathways have been implicated in various diseases, including autoimmune disorders, inflammatory diseases, and cancer.'
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Proteins (2)

Compounds (10)