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| | <StructureSection load='5ur7' size='340' side='right'caption='[[5ur7]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='5ur7' size='340' side='right'caption='[[5ur7]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ur7]] 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=5UR7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UR7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ur7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UR7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UR7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.0004Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCL20, LARC, MIP3A, SCYA20 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></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=5ur7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ur7 OCA], [http://pdbe.org/5ur7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ur7 RCSB], [http://www.ebi.ac.uk/pdbsum/5ur7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ur7 ProSAT]</span></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=5ur7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ur7 OCA], [https://pdbe.org/5ur7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ur7 RCSB], [https://www.ebi.ac.uk/pdbsum/5ur7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ur7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CCL20_HUMAN CCL20_HUMAN]] Chemotactic factor that attracts lymphocytes and, slightly, neutrophils, but not monocytes. Inhibits proliferation of myeloid progenitors in colony formation assays. May be involved in formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells. C-terminal processed forms have been shown to be equally chemotactically active for leukocytes. Possesses antibacterial activity E.coli ATCC 25922 and S.aureus ATCC 29213.<ref>PMID:12149255</ref> | + | [https://www.uniprot.org/uniprot/CCL20_HUMAN CCL20_HUMAN] Chemotactic factor that attracts lymphocytes and, slightly, neutrophils, but not monocytes. Inhibits proliferation of myeloid progenitors in colony formation assays. May be involved in formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells. C-terminal processed forms have been shown to be equally chemotactically active for leukocytes. Possesses antibacterial activity E.coli ATCC 25922 and S.aureus ATCC 29213.<ref>PMID:12149255</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Getschman, A E]] | + | [[Category: Getschman AE]] |
| - | [[Category: Peterson, F C]] | + | [[Category: Peterson FC]] |
| - | [[Category: Volkman, B F]] | + | [[Category: Volkman BF]] |
| - | [[Category: Ccl20]]
| + | |
| - | [[Category: Chemokine]]
| + | |
| - | [[Category: Chemotaxis]]
| + | |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Locked dimer]]
| + | |
| - | [[Category: Macrophage inflammatory protein-3 alpha]]
| + | |
| - | [[Category: Mip3-alpha]]
| + | |
| - | [[Category: Psoriasis]]
| + | |
| Structural highlights
Function
CCL20_HUMAN Chemotactic factor that attracts lymphocytes and, slightly, neutrophils, but not monocytes. Inhibits proliferation of myeloid progenitors in colony formation assays. May be involved in formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells. C-terminal processed forms have been shown to be equally chemotactically active for leukocytes. Possesses antibacterial activity E.coli ATCC 25922 and S.aureus ATCC 29213.[1]
Publication Abstract from PubMed
Psoriasis is a chronic inflammatory skin disease characterized by the infiltration of T cell and other immune cells to the skin in response to injury or autoantigens. Conventional, as well as unconventional, gammadelta T cells are recruited to the dermis and epidermis by CCL20 and other chemokines. Together with its receptor CCR6, CCL20 plays a critical role in the development of psoriasiform dermatitis in mouse models. We screened a panel of CCL20 variants designed to form dimers stabilized by intermolecular disulfide bonds. A single-atom substitution yielded a CCL20 variant (CCL20 S64C) that acted as a partial agonist for the chemokine receptor CCR6. CCL20 S64C bound CCR6 and induced intracellular calcium release, consistent with G-protein activation, but exhibited minimal chemotactic activity. Instead, CCL20 S64C inhibited CCR6-mediated T cell migration with nominal impact on other chemokine receptor signaling. When given in an IL-23-dependent mouse model for psoriasis, CCL20 S64C prevented psoriatic inflammation and the up-regulation of IL-17A and IL-22. Our results validate CCR6 as a tractable therapeutic target for psoriasis and demonstrate the value of CCL20 S64C as a lead compound.
Protein engineering of the chemokine CCL20 prevents psoriasiform dermatitis in an IL-23-dependent murine model.,Getschman AE, Imai Y, Larsen O, Peterson FC, Wu X, Rosenkilde MM, Hwang ST, Volkman BF Proc Natl Acad Sci U S A. 2017 Nov 6. pii: 201704958. doi:, 10.1073/pnas.1704958114. PMID:29109267[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hoover DM, Boulegue C, Yang D, Oppenheim JJ, Tucker K, Lu W, Lubkowski J. The structure of human macrophage inflammatory protein-3alpha /CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins. J Biol Chem. 2002 Oct 4;277(40):37647-54. Epub 2002 Jul 30. PMID:12149255 doi:10.1074/jbc.M203907200
- ↑ Getschman AE, Imai Y, Larsen O, Peterson FC, Wu X, Rosenkilde MM, Hwang ST, Volkman BF. Protein engineering of the chemokine CCL20 prevents psoriasiform dermatitis in an IL-23-dependent murine model. Proc Natl Acad Sci U S A. 2017 Nov 6. pii: 201704958. doi:, 10.1073/pnas.1704958114. PMID:29109267 doi:http://dx.doi.org/10.1073/pnas.1704958114
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