Monocyte chemoattractant protein: Difference between revisions
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<StructureSection load=' | <StructureSection load='' size='350' side='right' caption='Monocyte chemoattractant protein 1 complex with sulfate (PDB code [[1dok]])' scene='72/721520/Cv/2'> | ||
== Function == | == Function and Structure == | ||
''' | Human synthetic '''monocyte chemoattractant protein 1 (MCP)''' belongs to the superfamily of chemokines, which are proteins involved in immunoregulatory and inflammatory processes. The gene for CCL2 is on chromosome 17 in region 17q11.2-q12. The superfamily can be subdivided into 4 smaller groups, depending on the N-terminal arrangement of the cysteines. The CCL2<ref>PMID:8170963</ref> is also known as '''chemokine (C-C motif) ligand''' or: | ||
- MCP1 | - MCP1 | ||
- small inducible cytokine A2 (SCYA2) | - small inducible cytokine A2 (SCYA2) | ||
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- HC11. | - HC11. | ||
It exists as a monomer or a dimer, | It exists as a monomer or a dimer, even though the homodimer form is preferred. | ||
The structure of the monomer is made of <scene name='72/721520/Ligand_binding_on_ccl2/2'>3 Beta sheets and 1 alpha helix</scene>. | |||
*'''MCP-1''' regulates migration and infiltration of monocytes/macrophages<ref>PMID:19441883</ref>. | |||
*'''MCP-3''' activates all types of leukocytes<ref>PMID:11781181</ref>. | |||
*'''MCP-4''' is a potent chemoattractant for monocytes and eosinophils and stimulates histamine release from basophils<ref>PMID:8955214</ref>. | |||
== Ligands == | == Ligands == | ||
The known ligands for CCL2 are <scene name='72/721520/Ligand_binding_on_ccl2/1'>Potassium and PO4</scene>. The potassium binds to the S33 and S34 of the monomer and PO4 binds to F15 and N17. | |||
== | == Diseases == | ||
CCL2 is implicated in several diseases like psoriasis and rheumatoid arthritis where the appear to recruit macrophages, therefore bolstering the inflammation on joints. | |||
It is thought to be involved in atherosclerosis in the recruitment of monocytes into the arterial wall as well as in prostate cancer<ref>PMID:25917126</ref>. | |||
It has also been found elevated in the urine of people with lupus as a sign warning of inflammation of the kidney. | |||
CCL2 is overexpressed in epilepsy, brain ischemia, Alzheimer's disease, EAE and traumatic brain injury. | CCL2 is overexpressed in epilepsy, brain ischemia, Alzheimer's disease, EAE and traumatic brain injury. | ||
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Post translational modifications at the N-terminus can regulate receptor and target cell selectivity. Deletion of the N-terminal residue converts it from an activator of basophil to an eosinophil chemoattractant. | Post translational modifications at the N-terminus can regulate receptor and target cell selectivity. Deletion of the N-terminal residue converts it from an activator of basophil to an eosinophil chemoattractant. | ||
</StructureSection> | </StructureSection> | ||
[[Image:chaine.png]] | |||
== Synthesis == | |||
The protein human CCL2 has been synthesized using a combination of solid phase peptide synthesis (SPPS) and native chemical ligation (NCL). The thioester-peptide segment was synthesized using the sulfonamide safety-catch linker and 9-fluorenylmethoxycarbonyl (Fmoc) SPPS, and pseudoproline dipeptides were used to facilitate the synthesis of both CCL2 fragments. After assembly of the full-length peptide chain by NCL, a glutathione redox buffer was used to fold and oxidize the CCL2 protein. | |||
CCL2 was crystallized and the structure was determined by X-ray diffraction at 1.9-A resolution. This is probably one of the first crystal structures of a protein prepared using the sulfonamide safety-catch linker and NCL. | |||
==3D structures of Monocyte chemoattractant protein== | ==3D structures of Monocyte chemoattractant protein== | ||
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{{#tree:id=OrganizedByTopic|openlevels=0| | {{#tree:id=OrganizedByTopic|openlevels=0| | ||
* Monocyte chemoattractant protein 1 | * Monocyte chemoattractant protein 1 1 or C-C motif chemokine 2 or CCL2 | ||
**[[1dok]], [[1dol]] – hMCP-1 (mutant) - human<br /> | **[[1dok]], [[1dol]] – hMCP-1 (mutant) - human<br /> | ||
**[[1dom]], [[1don]] – hMCP-1 - NMR<br /> | **[[1dom]], [[1don]] – hMCP-1 - NMR<br /> | ||
**[[1ml0]], [[2nz1]] – hMCP-1 (mutant) + M3 protein<br /> | **[[1ml0]], [[2nz1]] – hMCP-1 (mutant) + M3 protein<br /> | ||
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**[[4zk9]] – hMCP-1 + chemokine binding protein<br /> | **[[4zk9]] – hMCP-1 + chemokine binding protein<br /> | ||
**[[4r8i]] – hMCP-1 + RNA<br /> | **[[4r8i]] – hMCP-1 + RNA<br /> | ||
**[[7so0]], [[8fj0]] – hMCP-1 + evasin<br /> | |||
* Monocyte chemoattractant protein 2 | * Monocyte chemoattractant protein 2 or CCL8 or C-C motif chemokine 8 | ||
**[[7s5a]] – hMCP-2 <br /> | |||
**[[1esr]] – hMCP-2 (mutant) <br /> | **[[1esr]] – hMCP-2 (mutant) <br /> | ||
* Monocyte chemoattractant protein 3 | * Monocyte chemoattractant protein 3 or C-C motif chemokine 7 or CCL7 | ||
**[[1ncv]], [[1bo0]] – hMCP-3 - NMR<br /> | **[[1ncv]], [[1bo0]] – hMCP-3 - NMR<br /> | ||
**[[4zkc]] – hMCP-3 + chemokine binding protein<br /> | **[[4zkc]] – hMCP-3 + chemokine binding protein<br /> | ||
**[[7s58]], [[7s59]], [[7scu]] – hMCP-3 + evasin<br /> | |||
**[[8fk6]], [[8fk8]] – hMCP-3 + evasin<br /> | |||
**[[8fj3]] – hMCP-3 (mutant) + evasin<br /> | |||
* Monocyte chemoattractant protein 4 | * Monocyte chemoattractant protein 4 | ||
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http://www.rcsb.org/pdb/explore/explore.do?structureId=3IFD | http://www.rcsb.org/pdb/explore/explore.do?structureId=3IFD | ||
<references/> | <references/> | ||
[[Category:Topic Page]] | |||