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| | <StructureSection load='4r8i' size='340' side='right'caption='[[4r8i]], [[Resolution|resolution]] 2.05Å' scene=''> | | <StructureSection load='4r8i' size='340' side='right'caption='[[4r8i]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4r8i]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R8I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4r8i]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R8I FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SR:STRONTIUM+ION'>SR</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0A:L-ADENOSINE-5-MONOPHOSPHATE'>0A</scene>, <scene name='pdbligand=0C:L-CYTIDINE-5-MONOPHOSPHATE'>0C</scene>, <scene name='pdbligand=0G:L-GUANOSINE-5-MONOPHOSPHATE'>0G</scene>, <scene name='pdbligand=0U:L-URIDINE-5-MONOPHOSPHATE'>0U</scene>, <scene name='pdbligand=0U1:2-METHYLSELENYL-2-DEOXY-L-URIDINE-5-MONOPHOSPHATE'>0U1</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SR:STRONTIUM+ION'>SR</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=0A:L-ADENOSINE-5-MONOPHOSPHATE'>0A</scene>, <scene name='pdbligand=0C:L-CYTIDINE-5-MONOPHOSPHATE'>0C</scene>, <scene name='pdbligand=0G:L-GUANOSINE-5-MONOPHOSPHATE'>0G</scene>, <scene name='pdbligand=0U:L-URIDINE-5-MONOPHOSPHATE'>0U</scene>, <scene name='pdbligand=0U1:2-METHYLSELENYL-2-DEOXY-L-URIDINE-5-MONOPHOSPHATE'>0U1</scene></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4r8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r8i OCA], [https://pdbe.org/4r8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r8i RCSB], [https://www.ebi.ac.uk/pdbsum/4r8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r8i ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCL2, MCP1, SCYA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4r8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r8i OCA], [http://pdbe.org/4r8i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r8i RCSB], [http://www.ebi.ac.uk/pdbsum/4r8i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r8i ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CCL2_HUMAN CCL2_HUMAN]] Chemotactic factor that attracts monocytes and basophils but not neutrophils or eosinophils. Augments monocyte anti-tumor activity. Has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis or atherosclerosis. May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis. | + | [https://www.uniprot.org/uniprot/CCL2_HUMAN CCL2_HUMAN] Chemotactic factor that attracts monocytes and basophils but not neutrophils or eosinophils. Augments monocyte anti-tumor activity. Has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis or atherosclerosis. May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| | *[[Monocyte chemoattractant protein|Monocyte chemoattractant protein]] | | *[[Monocyte chemoattractant protein|Monocyte chemoattractant protein]] |
| - | *[[User:Coline Perrin/CCL2|User:Coline Perrin/CCL2]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Achenbach, J]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Betzel, C]] | + | [[Category: Achenbach J]] |
| - | [[Category: Buchner, K]] | + | [[Category: Betzel C]] |
| - | [[Category: Falke, S]] | + | [[Category: Buchner K]] |
| - | [[Category: Gabdulkhakov, A]] | + | [[Category: Falke S]] |
| - | [[Category: Klussmann, S]] | + | [[Category: Gabdulkhakov A]] |
| - | [[Category: Maasch, C]] | + | [[Category: Klussmann S]] |
| - | [[Category: Oberthuer, D]] | + | [[Category: Maasch C]] |
| - | [[Category: Rehders, D]] | + | [[Category: Oberthuer D]] |
| - | [[Category: Aptamer spiegelmer l-oligonucleotide]]
| + | [[Category: Rehders D]] |
| - | [[Category: Cytokine-rna complex]]
| + | |
| Structural highlights
4r8i is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
CCL2_HUMAN Chemotactic factor that attracts monocytes and basophils but not neutrophils or eosinophils. Augments monocyte anti-tumor activity. Has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis or atherosclerosis. May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis.
Publication Abstract from PubMed
We report the crystal structure of a 40mer mirror-image RNA oligonucleotide completely built from nucleotides of the non-natural L-chirality in complex with the pro-inflammatory chemokine L-CLL2 (monocyte chemoattractant protein-1), a natural protein composed of regular L-amino acids. The L-oligonucleotide is an L-aptamer (a Spiegelmer) identified to bind L-CCL2 with high affinity, thereby neutralizing the chemokine's activity. CCL2 plays a key role in attracting and positioning monocytes; its overexpression in several inflammatory diseases makes CCL2 an interesting pharmacological target. The PEGylated form of the L-aptamer, NOX-E36 (emapticap pegol), already showed promising efficacy in clinical Phase II studies conducted in diabetic nephropathy patients. The structure of the L-oligonucleotide.L-protein complex was solved and refined to 2.05 A. It unveils the L-aptamer's intramolecular contacts and permits a detailed analysis of its structure-function relationship. Furthermore, the analysis of the intermolecular drug-target interactions reveals insight into the selectivity of the L-aptamer for certain related chemokines.
Crystal structure of a mirror-image L-RNA aptamer (Spiegelmer) in complex with the natural L-protein target CCL2.,Oberthur D, Achenbach J, Gabdulkhakov A, Buchner K, Maasch C, Falke S, Rehders D, Klussmann S, Betzel C Nat Commun. 2015 Apr 22;6:6923. doi: 10.1038/ncomms7923. PMID:25901662[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Oberthur D, Achenbach J, Gabdulkhakov A, Buchner K, Maasch C, Falke S, Rehders D, Klussmann S, Betzel C. Crystal structure of a mirror-image L-RNA aptamer (Spiegelmer) in complex with the natural L-protein target CCL2. Nat Commun. 2015 Apr 22;6:6923. doi: 10.1038/ncomms7923. PMID:25901662 doi:http://dx.doi.org/10.1038/ncomms7923
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