User:Coline Perrin/CCL2: Difference between revisions

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~~==Introduction==~~

== Function and Structure ==

The''' chemokine (C-C motif) ligand''' ~~(CCL2), also known as~~ :

- ~~monocyte chemotactic protein 1 (~~MCP1)

'''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<ref>PMID:8170963</ref> is also known as '''chemokine (C-C motif) ligand''' or:

- MCP1

- small inducible cytokine A2 (SCYA2)

- MCAF

Line 11:

Line 12:

- GDCF-2

- HC11.

~~== Function ==~~

== ~~Disease~~ ==

It exists as a monomer or a dimer, eventhough 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>.

== 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.

== Evolutionary Conservation ==

[[Image:Consurf_key_small.gif|200px|right]]

Check<jmol>

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/if/3ifd_consurf.spt"</scriptWhenChecked>

<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>

<text>to colour the structure by Evolutionary Conservation</text>

</jmolCheckbox>

</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB].

== Diseases ==

~~== Relevance ==~~

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.

== Structural highlights ==

CCL2 belongs to the superfamily of chemokines, which are proteins involved in immunoregulatory and inflammatory processes. The superfamily can be subdivided into 4 smaller groups, depending on the N-ter arangment of the cysteines. CCL2 is part of the C-C motif group because of the covalent bond made between 2 of the 4 cysteines of the ~~Nter~~ domain.

CCL2 is part of the C-C motif group because of the covalent bond made between <scene name='72/721520/Cv/4'>2 of the 4 cysteines of the N terminal domain</scene>.<ref>PMID:8989326</ref>

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>

[[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==

Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}

{{#tree:id=OrganizedByTopic|openlevels=0|

* Monocyte chemoattractant protein 1

**[[1dok]], [[1dol]] – hMCP-1 (mutant) - human<br />

**[[3ifd]] – hMCP-1 <br />

**[[1dom]], [[1don]] – hMCP-1 - NMR<br />

**[[1ml0]], [[2nz1]] – hMCP-1 (mutant) + M3 protein<br />

**[[2bdn]] – hMCP-1 + antibody<br />

**[[4dn4]] – hMCP-1 (mutant) + antibody<br />

**[[4zk9]] – hMCP-1 + chemokine binding protein<br />

**[[4r8i]] – hMCP-1 + RNA<br />

* Monocyte chemoattractant protein 2

**[[1esr]] – hMCP-2 (mutant) <br />

* Monocyte chemoattractant protein 3

**[[1ncv]], [[1bo0]] – hMCP-3 - NMR<br />

**[[4zkc]] – hMCP-3 + chemokine binding protein<br />

* Monocyte chemoattractant protein 4

**[[2ra4]] – hMCP-4 <br />

}}

== 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

@@ Line 1: / Line 1: @@
-==Introduction==
+<StructureSection load='1dok' size='350' side='right' caption='Monocyte chemoattractant protein 1 (PDB code [[3idf]])' scene='72/721520/Cv/2'>
-<StructureSection load='1dok' size='340' side='right' caption='Caption for this structure' scene=''>
+== Function and Structure ==
-The''' chemokine (C-C motif) ligand''' (CCL2), also known as :
-- monocyte chemotactic protein 1 (MCP1)
+'''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<ref>PMID:8170963</ref> is also known as '''chemokine (C-C motif) ligand''' or:
+- MCP1
 - small inducible cytokine A2 (SCYA2)
 - MCAF
@@ Line 11: / Line 12: @@
 - GDCF-2
 - HC11.
-== Function ==
-== Disease ==
+It exists as a monomer or a dimer, eventhough 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>.
+== 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.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/if/3ifd_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Diseases ==
-== Relevance ==
+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.
 == Structural highlights ==
-CCL2 belongs to the superfamily of chemokines, which are proteins involved in immunoregulatory and inflammatory processes. The superfamily can be subdivided into 4 smaller groups, depending on the N-ter arangment of the cysteines. CCL2 is part of the C-C motif group because of the covalent bond made between 2 of the 4 cysteines of the Nter domain.
+CCL2 is part of the C-C motif group because of the covalent bond made between <scene name='72/721520/Cv/4'>2 of the 4 cysteines of the N terminal domain</scene>.<ref>PMID:8989326</ref>
+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>
+[[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==
+Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
+{{#tree:id=OrganizedByTopic|openlevels=0|
+* Monocyte chemoattractant protein 1
+**[[1dok]], [[1dol]] – hMCP-1 (mutant) - human<br />
+**[[3ifd]] – hMCP-1 <br />
+**[[1dom]], [[1don]] – hMCP-1 - NMR<br />
+**[[1ml0]], [[2nz1]] – hMCP-1 (mutant) + M3 protein<br />
+**[[2bdn]] – hMCP-1 + antibody<br />
+**[[4dn4]] – hMCP-1 (mutant) + antibody<br />
+**[[4zk9]] – hMCP-1 + chemokine binding protein<br />
+**[[4r8i]] – hMCP-1 + RNA<br />
+* Monocyte chemoattractant protein 2
+**[[1esr]] – hMCP-2 (mutant) <br />
+* Monocyte chemoattractant protein 3
+**[[1ncv]], [[1bo0]] – hMCP-3 - NMR<br />
+**[[4zkc]] – hMCP-3 + chemokine binding protein<br />
+* Monocyte chemoattractant protein 4
+**[[2ra4]] – hMCP-4 <br />
+}}
 == 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
 <references/>