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| | <StructureSection load='4mhe' size='340' side='right'caption='[[4mhe]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='4mhe' size='340' side='right'caption='[[4mhe]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4mhe]] is a 4 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=4MHE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MHE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4mhe]] is a 4 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=4MHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MHE 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></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]] 2.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCL18, AMAC1, DCCK1, MIP4, PARC, SCYA18 ([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></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=4mhe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mhe OCA], [http://pdbe.org/4mhe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mhe RCSB], [http://www.ebi.ac.uk/pdbsum/4mhe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mhe 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=4mhe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mhe OCA], [https://pdbe.org/4mhe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mhe RCSB], [https://www.ebi.ac.uk/pdbsum/4mhe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mhe ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CCL18_HUMAN CCL18_HUMAN]] Chemotactic factor that attracts lymphocytes but not monocytes or granulocytes. May be involved in B-cell migration into B-cell follicles in lymph nodes. Attracts naive T-lymphocytes toward dendritic cells and activated macrophages in lymph nodes, has chemotactic activity for naive T-cells, CD4+ and CD8+ T-cells and thus may play a role in both humoral and cell-mediated immunity responses.<ref>PMID:11745396</ref> <ref>PMID:11978786</ref> | + | [https://www.uniprot.org/uniprot/CCL18_HUMAN CCL18_HUMAN] Chemotactic factor that attracts lymphocytes but not monocytes or granulocytes. May be involved in B-cell migration into B-cell follicles in lymph nodes. Attracts naive T-lymphocytes toward dendritic cells and activated macrophages in lymph nodes, has chemotactic activity for naive T-cells, CD4+ and CD8+ T-cells and thus may play a role in both humoral and cell-mediated immunity responses.<ref>PMID:11745396</ref> <ref>PMID:11978786</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: Liang, W G]] | + | [[Category: Liang WG]] |
| - | [[Category: Tang, W J]] | + | [[Category: Tang W-J]] |
| - | [[Category: Greek key shape]]
| + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
Function
CCL18_HUMAN Chemotactic factor that attracts lymphocytes but not monocytes or granulocytes. May be involved in B-cell migration into B-cell follicles in lymph nodes. Attracts naive T-lymphocytes toward dendritic cells and activated macrophages in lymph nodes, has chemotactic activity for naive T-cells, CD4+ and CD8+ T-cells and thus may play a role in both humoral and cell-mediated immunity responses.[1] [2]
Publication Abstract from PubMed
CC chemokine ligands (CCLs) are 8- to 14-kDa signaling proteins involved in diverse immune functions. While CCLs share similar tertiary structures, oligomerization produces highly diverse quaternary structures that protect chemokines from proteolytic degradation and modulate their functions. CCL18 is closely related to CCL3 and CCL4 with respect to both protein sequence and genomic location, yet CCL18 has distinct biochemical and biophysical properties. Here, we report a crystal structure of human CCL18 and its oligomerization states in solution based on crystallographic and small-angle X-ray scattering analyses. Our data show that CCL18 adopts an alpha-helical conformation at its N-terminus that weakens its dimerization, explaining CCL18's preference for the monomeric state. Multiple contacts between monomers allow CCL18 to reversibly form a unique open-ended oligomer different from those of CCL3, CCL4, and CCL5. Furthermore, these differences hinge on proline 8, which is conserved in CCL3 and CCL4 but is replaced by lysine in human CCL18. Our structural analyses suggest that a mutation of proline 8 to alanine stabilizes a type 1 beta-turn at the N-terminus of CCL4 to prevent dimerization but prevents dimers from making key contacts with each other in CCL3. Thus, the P8A mutation induces depolymerization of CCL3 and CCL4 by distinct mechanisms. Finally, we used structural, biochemical, and functional analyses to unravel why insulin-degrading enzyme degrades CCL3 and CCL4 but not CCL18. Our results elucidate the molecular basis for the oligomerization of three closely related CC chemokines and suggest how oligomerization shapes CCL chemokine function.
Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme.,Liang WG, Ren M, Zhao F, Tang WJ J Mol Biol. 2015 Mar 27;427(6 Pt B):1345-58. doi: 10.1016/j.jmb.2015.01.012. Epub, 2015 Jan 28. PMID:25636406[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Schutyser E, Struyf S, Wuyts A, Put W, Geboes K, Grillet B, Opdenakker G, Van Damme J. Selective induction of CCL18/PARC by staphylococcal enterotoxins in mononuclear cells and enhanced levels in septic and rheumatoid arthritis. Eur J Immunol. 2001 Dec;31(12):3755-62. PMID:11745396 doi:http://dx.doi.org/10.1002/1521-4141(200112)31:12<3755::AID-IMMU3755>3.0.CO;2-O
- ↑ Schutyser E, Struyf S, Proost P, Opdenakker G, Laureys G, Verhasselt B, Peperstraete L, Van de Putte I, Saccani A, Allavena P, Mantovani A, Van Damme J. Identification of biologically active chemokine isoforms from ascitic fluid and elevated levels of CCL18/pulmonary and activation-regulated chemokine in ovarian carcinoma. J Biol Chem. 2002 Jul 5;277(27):24584-93. Epub 2002 Apr 26. PMID:11978786 doi:http://dx.doi.org/10.1074/jbc.M112275200
- ↑ Liang WG, Ren M, Zhao F, Tang WJ. Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme. J Mol Biol. 2015 Mar 27;427(6 Pt B):1345-58. doi: 10.1016/j.jmb.2015.01.012. Epub, 2015 Jan 28. PMID:25636406 doi:http://dx.doi.org/10.1016/j.jmb.2015.01.012
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