Target type: molecularfunction
Binding to chemokine (C-C motif) ligand 7. [GOC:BHF]
Chemokine (C-C motif) ligand 7 (CCL7), also known as monocyte chemoattractant protein 3 (MCP-3), is a small cytokine belonging to the CC chemokine family. It plays a critical role in the recruitment and activation of immune cells, particularly monocytes, macrophages, and T lymphocytes.
CCL7 exerts its biological effects by binding to its cognate receptor, CCR1, a G protein-coupled receptor (GPCR) expressed on the surface of immune cells. This binding event triggers a cascade of intracellular signaling events, leading to the activation of various downstream pathways.
**Molecular Function of CCL7 Binding to CCR1:**
1. **Ligand Binding and Receptor Activation:** CCL7 binds to the extracellular domain of CCR1, inducing a conformational change in the receptor that activates its intracellular signaling domains.
2. **G Protein Coupling:** The activated CCR1 receptor interacts with heterotrimeric G proteins, leading to the dissociation of the Gα subunit from the Gβγ dimer.
3. **Signaling Cascades:** The Gα subunit activates downstream signaling pathways, including the phospholipase C (PLC) pathway and the mitogen-activated protein kinase (MAPK) pathway.
4. **Calcium Mobilization:** PLC activation leads to the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into diacylglycerol (DAG) and inositol trisphosphate (IP3). IP3 triggers the release of calcium ions (Ca2+) from intracellular stores.
5. **Cell Migration and Chemotaxis:** The increased intracellular Ca2+ concentration and activation of the MAPK pathway contribute to cytoskeletal rearrangements and the formation of lamellipodia, promoting cell migration towards the CCL7 source.
6. **Activation of Immune Cells:** CCL7 binding to CCR1 triggers the release of pro-inflammatory cytokines, chemokines, and other mediators, leading to the activation and differentiation of immune cells.
**In summary, the binding of CCL7 to CCR1 initiates a complex signaling cascade that ultimately leads to the recruitment and activation of immune cells, contributing to the inflammatory response and immune homeostasis.**'
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Protein | Definition | Taxonomy |
---|---|---|
C-C chemokine receptor type 2 | A C-C chemokine receptor type 2 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P41597] | Homo sapiens (human) |
C-C chemokine receptor type 1 | A C-C chemokine receptor type 1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P32246] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
1,10-phenanthroline | 1,10-phenanthroline: RN given refers to parent cpd; inhibits Zn-dependent metalloproteinases | phenanthroline | EC 2.7.1.1 (hexokinase) inhibitor; EC 3.4.19.3 (pyroglutamyl-peptidase I) inhibitor |
2,2'-dipyridyl | 2,2'-bipyridine : A bipyridine in which the two pyridine moieties are linked by a bond between positions C-2 and C-2'. 2,2'-Dipyridyl: A reagent used for the determination of iron. | bipyridine | chelator; ferroptosis inhibitor |
amiodarone | amiodarone : A member of the class of 1-benzofurans that is 1-benzofuran substituted by a butyl group at position 2 and a 4-[2-(diethylamino)ethoxy]-3,5-diiodobenzoyl group at position 3. It is a cardiovascular drug used for the treatment of cardiac dysrhythmias. Amiodarone: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance. | 1-benzofurans; aromatic ketone; organoiodine compound; tertiary amino compound | cardiovascular drug |
disulfiram | organic disulfide; organosulfur acaricide | angiogenesis inhibitor; antineoplastic agent; apoptosis inducer; EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor; EC 3.1.1.1 (carboxylesterase) inhibitor; EC 3.1.1.8 (cholinesterase) inhibitor; EC 5.99.1.2 (DNA topoisomerase) inhibitor; ferroptosis inducer; fungicide; NF-kappaB inhibitor | |
fasudil | fasudil : An isoquinoline substituted by a (1,4-diazepan-1-yl)sulfonyl group at position 5. It is a Rho-kinase inhibitor and its hydrochloride hydrate form is approved for the treatment of cerebral vasospasm and cerebral ischemia. fasudil: intracellular calcium antagonist; structure in first source | isoquinolines; N-sulfonyldiazepane | antihypertensive agent; calcium channel blocker; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; geroprotector; neuroprotective agent; nootropic agent; vasodilator agent |
nifedipine | Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. | C-nitro compound; dihydropyridine; methyl ester | calcium channel blocker; human metabolite; tocolytic agent; vasodilator agent |
dibenzothiazyl disulfide | dibenzothiazol-2-yl disulfide : An organic disulfide resulting from the formal oxidative coupling of the thiol groups of two molecules of 1,3-benzothiazole-2-thiol. It is used as an accelerator in the rubber industry. dibenzothiazyl disulfide: vulcanizing accelerant | benzothiazoles; organic disulfide | allergen |
1-naphthylisothiocyanate | 1-Naphthylisothiocyanate: A tool for the study of liver damage which causes bile stasis and hyperbilirubinemia acutely and bile duct hyperplasia and biliary cirrhosis chronically, with changes in hepatocyte function. It may cause skin and kidney damage. | isothiocyanate | insecticide |
4,4'-dimethyl-2,2'-bipyridine | 4,4'-dimethyl-2,2'-bipyridine: structure in first source | ||
5,5'-dimethyl-2,2'-bipyridyl | 5,5'-dimethyl-2,2'-bipyridyl: structure in first source | bipyridines | |
plerixafor | plerixafor : An azamacrocycle consisting of two cyclam rings connected by a 1,4-phenylenebis(methylene) linker. It is a CXCR4 chemokine receptor antagonist and a hematopoietic stem cell mobilizer. It is used in combination with grulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the perpheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma. plerixafor: a bicyclam derivate, highly potent & selective inhibitor of HIV-1 & HIV-2 | azacycloalkane; azamacrocycle; benzenes; crown amine; secondary amino compound; tertiary amino compound | anti-HIV agent; antineoplastic agent; C-X-C chemokine receptor type 4 antagonist; immunological adjuvant |
neocuproine | neocuproine : A member of the class of phenanthrolines that is 1,10-phenanthroline bearing two methyl substituents at positions 2 and 9. neocuproine: Spectrophotometric determination of copper and ultramicro blood sugar determinations; structure; RN given refers to parent cpd | phenanthrolines | chelator; copper chelator |
2,2',2''-terpyridine | 2,2',2''-terpyridine: RN given refers to parent cpd 2,2':6',2''-terpyridine : A tridentate heterocyclic ligand that binds metals at three meridional sites giving two adjacent 5-membered MN2C2 chelate rings. | terpyridines | chelator |
5-methyl-1,10-phenanthroline | |||
3,4,7,8-tetramethyl-1,10-phenanthroline | |||
rosiglitazone | aminopyridine; thiazolidinediones | EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor; ferroptosis inhibitor; insulin-sensitizing drug | |
fasudil hydrochloride | fasudil hydrochloride : A hydrochloride obtained by reaction of fasudil with one equivalent of hydrochloric acid. | hydrochloride | antihypertensive agent; calcium channel blocker; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; neuroprotective agent; nootropic agent; vasodilator agent |
tak 779 | |||
bx 471 | BX 471: a CC chemokine receptor-1 antagonist; structure in first source | ||
cp 481715 | quinoxaline-2-carboxylic acid (4-carbamoyl-1-(3-fluorobenzyl)-2,7-dihydroxy-7-methyloctyl)amide: a CCR1 antagonist and NSAID; structure in first source | ||
bay 11-7085 | BAY11-7085 : A sulfone that is benzene substituted by [(E)-2-cyanoethenyl]sulfonyl and tert-butyl groups at position 1 and 4, respectively. It is an irreversible inhibitor of IkappaB-alpha phosphorylation in cells (IC50 = 10 muM) and prevents the activation of NF-kappaB. | benzenes; nitrile; sulfone | anti-inflammatory agent; antibacterial agent; antineoplastic agent; apoptosis inducer; autophagy inducer; EC 2.7.11.10 (IkappaB kinase) inhibitor; ferroptosis inducer; NF-kappaB inhibitor |
ucb 35625 | UCB 35625: J-113863 is the (trans)-isomer; structure in first source | ||
vuf 2274 | 5-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2,2-diphenylpentanenitrile: an inverse agonist of human cytomegalovirus; structure in first source | ||
rs 504393 | RS 504393: structure in first source | 1,3-oxazoles | |
incb3344 | INCB3344: potent and selective small molecule CCR2 chemokine receptor antagonist | ||
amd 070 | mavorixafor: a derivative of AMD3100; a CXCR4 blocker | aminoquinoline | |
cenicriviroc | cenicriviroc : A member of the class of benzazocines that is (5Z)-1,2,3,4-tetrahydro-1-benzazocine which is substituted by a 2-methylpropyl, N-{4-[(S)-(1-propyl-1H-imidazol-5-yl)methanesulfinyl]phenyl}carboxamide and 4-(2-butoxyethoxy)phenyl groups at positions 1, 5 and 8, respectively. It is a potent chemokine 2 and 5 receptor antagonist currently in development for the treatment of liver fibrosis in adults with nonalcoholic steatohepatitis (NASH). cenicriviroc: an inhibitor of HIV-1 | aromatic ether; benzazocine; diether; imidazoles; secondary carboxamide; sulfoxide | anti-HIV agent; anti-inflammatory agent; antirheumatic drug; chemokine receptor 2 antagonist; chemokine receptor 5 antagonist |
incb 3284 | INCB 3284: a CCR2 receptor antagonist | ||
azd8309 | AZD8309: CXCR2 inhibitor | ||
a 803467 | A 803467: an Nav1.8 sodium channel blocker; structure in first source | ||
n-(carbamoylmethyl)-3-trifluoromethyl benzamido-4-chlorobenzyl 3-aminopyrrolidine | |||
raltegravir | 1,2,4-oxadiazole; dicarboxylic acid amide; hydroxypyrimidine; monofluorobenzenes; pyrimidone; secondary carboxamide | antiviral drug; HIV-1 integrase inhibitor |