Page last updated: 2024-10-24

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)

ProteinDefinitionTaxonomy
Interleukin-8An interleukin-8 that is encoded in the genome of human. [PMID:15623624, SALO:AJ]Homo sapiens (human)
Stromal cell-derived factor 1A stromal cell-derived factor 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P48061]Homo sapiens (human)

Compounds (10)

CompoundDefinitionClassesRoles
diclofenacdiclofenac : A monocarboxylic acid consisting of phenylacetic acid having a (2,6-dichlorophenyl)amino group at the 2-position.

Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.
amino acid;
aromatic amine;
dichlorobenzene;
monocarboxylic acid;
secondary amino compound
antipyretic;
drug allergen;
EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor;
environmental contaminant;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug;
xenobiotic
indomethacinindometacin : A member of the class of indole-3-acetic acids that is indole-3-acetic acid in which the indole ring is substituted at positions 1, 2 and 5 by p-chlorobenzoyl, methyl, and methoxy groups, respectively. A non-steroidal anti-inflammatory drug, it is used in the treatment of musculoskeletal and joint disorders including osteoarthritis, rheumatoid arthritis, gout, bursitis and tendinitis.

Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES.
aromatic ether;
indole-3-acetic acids;
monochlorobenzenes;
N-acylindole
analgesic;
drug metabolite;
EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor;
environmental contaminant;
gout suppressant;
non-steroidal anti-inflammatory drug;
xenobiotic;
xenobiotic metabolite
tolmetintolmetin : A monocarboxylic acid that is (1-methylpyrrol-2-yl)acetic acid substituted at position 5 on the pyrrole ring by a 4-methylbenzoyl group. Used in the form of its sodium salt dihydrate as a nonselective nonsteroidal anti-inflammatory drug.

Tolmetin: A non-steroidal anti-inflammatory agent (ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL) similar in mode of action to INDOMETHACIN.
aromatic ketone;
monocarboxylic acid;
pyrroles
EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor;
non-steroidal anti-inflammatory drug
ibufenacibufenac : A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is replaced by a 4-isobutylphenyl group. Although it was shown to be effective in treatment of rheumatoid arthritis, the clinical use of ibufenac was discontinued due to hepatotoxic side-effects.

ibufenac: used in the treatment of rheumatism; also possesses antipyretic properties; minor descriptor (75-84); on-line & Index Medicus search PHENYLACETATES (75-84); RN given refers to parent cpd
monocarboxylic acidEC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor;
hepatotoxic agent;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug
ibuprofen, (r)-isomeribuprofen
ketoprofen
chalconetrans-chalcone : The trans-isomer of chalcone.chalconeEC 3.2.1.1 (alpha-amylase) inhibitor
2-anilinophenylacetic acid2-anilinophenylacetic acid: structure in first source
4-hydroxychalcone4-hydroxychalcone : A member of the class of chalcones that is trans-chalcone substituted by a hydroxy group at position 4.

4-hydroxychalcone: structure in first source
chalcones;
phenols
antihypertensive agent;
plant metabolite
phenyl-3-methoxy-4-hydroxystyryl ketonephenyl-3-methoxy-4-hydroxystyryl ketone: structure given in first source