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.
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.
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-ter arangment of the cysteines. The CCL2[1] is also known as chemokine (C-C motif) ligand or:
- MCP1
- small inducible cytokine A2 (SCYA2)
- MCAF
- GDCF-2
- SMC-CF
- HSMCR30
- MGC9434
- GDCF-2
- HC11.
It exists as a monomer or a dimer, eventhough the homodimer form is preferred.
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[2].
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.
Structural highlights
CCL2 is part of the C-C motif group because of the covalent bond made between 2 of the 4 cysteines of the N terminal domain.[3]
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.
↑Carr MW, Roth SJ, Luther E, Rose SS, Springer TA. Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3652-6. PMID:8170963
↑Ito Y, Ishiguro H, Kobayashi N, Hasumi H, Watanabe M, Yao M, Uemura H. Adipocyte-derived monocyte chemotactic protein-1 (MCP-1) promotes prostate cancer progression through the induction of MMP-2 activity. Prostate. 2015 Jul 1;75(10):1009-19. doi: 10.1002/pros.22972. Epub 2015 Apr 27. PMID:25917126 doi:https://dx.doi.org/10.1002/pros.22972
↑Lubkowski J, Bujacz G, Boque L, Domaille PJ, Handel TM, Wlodawer A. The structure of MCP-1 in two crystal forms provides a rare example of variable quaternary interactions. Nat Struct Biol. 1997 Jan;4(1):64-9. PMID:8989326
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.
