Monocyte chemoattractant protein

From Proteopedia

Contents 1 Function and Structure 2 Ligands 3 Diseases 4 Structural highlights 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[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, even though the homodimer form is preferred. The structure of the monomer is made of 3 Beta sheets and 1 alpha helix. MCP-1 regulates migration and infiltration of monocytes/macrophages[2]. MCP-3 activates all types of leukocytes[3]. MCP-4 is a potent chemoattractant for monocytes and eosinophils and stimulates histamine release from basophils[4]. Ligands The known ligands for CCL2 are Potassium and PO4. 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[5]. 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.[6] 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.

spinqualitylabelsall models Monocyte chemoattractant protein 1 complex with sulfate (PDB code 1dok) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Updated on 15-July-2024

Monocyte chemoattractant protein 1 1 or C-C motif chemokine 2 or CCL2

1dok, 1dol – hMCP-1 (mutant) - human

1dom, 1don – hMCP-1 - NMR

1ml0, 2nz1 – hMCP-1 (mutant) + M3 protein

2bdn – hMCP-1 + antibody

4dn4 – hMCP-1 (mutant) + antibody

4zk9 – hMCP-1 + chemokine binding protein

4r8i – hMCP-1 + RNA

7so0, 8fj0 – hMCP-1 + evasin

Monocyte chemoattractant protein 2 or CCL8 or C-C motif chemokine 8

7s5a – hMCP-2

1esr – hMCP-2 (mutant)

Monocyte chemoattractant protein 3 or C-C motif chemokine 7 or CCL7

1ncv, 1bo0 – hMCP-3 - NMR

4zkc – hMCP-3 + chemokine binding protein

7s58, 7s59, 7scu – hMCP-3 + evasin

8fk6, 8fk8 – hMCP-3 + evasin

8fj3 – hMCP-3 (mutant) + evasin

Monocyte chemoattractant protein 4

2ra4 – hMCP-4

References

https://fr.wikipedia.org/wiki/CCL2 http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=1DOK http://www.uniprot.org/uniprot/P13500#interaction http://www.rcsb.org/pdb/explore/explore.do?structureId=3IFD

1. ↑ 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
2. ↑ Deshmane SL, Kremlev S, Amini S, Sawaya BE. Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res. 2009 Jun;29(6):313-26. PMID:19441883 doi:10.1089/jir.2008.0027
3. ↑ Menten P, Wuyts A, Van Damme J. Monocyte chemotactic protein-3. Eur Cytokine Netw. 2001 Oct-Dec;12(4):554-60 PMID:11781181
4. ↑ Garcia-Zepeda EA, Combadiere C, Rothenberg ME, Sarafi MN, Lavigne F, Hamid Q, Murphy PM, Luster AD. Human monocyte chemoattractant protein (MCP)-4 is a novel CC chemokine with activities on monocytes, eosinophils, and basophils induced in allergic and nonallergic inflammation that signals through the CC chemokine receptors (CCR)-2 and -3. J Immunol. 1996 Dec 15;157(12):5613-26 PMID:8955214
5. ↑ 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:http://dx.doi.org/10.1002/pros.22972
6. ↑ 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