Monocyte chemoattractant protein

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Revision as of 13:14, 26 January 2016

spinqualitylabelsall models Monocyte chemoattractant protein 1 (PDB code 3idf) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Ligands 3 Disease 4 Structural highlights Function HHuman 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. -> Binds to CCR2 and CCR4. Is tethered on endothelial cells by glycosaminoglycan (GAG) side chains of proteoglycans. Ligands K and PO4 Disease 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. 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] 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.

Synthesis

The protein human CC chemokine ligand 2 (CCL2, also known as monocyte chemoattractant protein 1 or MCP-1) 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. Synthetic human CCL2 binds to and activates the CCR2 receptor on THP-1 cells, as expected. CCL2 was crystallized and the structure was determined by X-ray diffraction at 1.9-A resolution. The structure of the synthetic protein is very similar to that of a previously reported structure of recombinant human CCL2, although the crystal form is different. The functional CCL2 dimer for the crystal structure reported here is formed around a crystallographic twofold axis. The dimer interface involves residues Val9-Thr10-Cys11, which form an intersubunit antiparallel beta-sheet. Comparison of the CCL2 dimers in different crystal forms indicates a significant flexibility of the quaternary structure. To our knowledge, this is 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 26-January-2016

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. ↑ 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