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| | <StructureSection load='5eki' size='340' side='right'caption='[[5eki]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='5eki' size='340' side='right'caption='[[5eki]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5eki]] is a 6 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=5EKI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EKI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5eki]] is a 6 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=5EKI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EKI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCL21, SCYA21, UNQ784/PRO1600 ([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=SO4:SULFATE+ION'>SO4</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=5eki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eki OCA], [http://pdbe.org/5eki PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eki RCSB], [http://www.ebi.ac.uk/pdbsum/5eki PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eki 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=5eki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eki OCA], [https://pdbe.org/5eki PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5eki RCSB], [https://www.ebi.ac.uk/pdbsum/5eki PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5eki ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CCL21_HUMAN CCL21_HUMAN]] Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Shows preferential activity towards naive T-cells. May play a role in mediating homing of lymphocytes to secondary lymphoid organs. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4. | + | [https://www.uniprot.org/uniprot/CCL21_HUMAN CCL21_HUMAN] Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Shows preferential activity towards naive T-cells. May play a role in mediating homing of lymphocytes to secondary lymphoid organs. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4. |
| | <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: Chen, Y]] | + | [[Category: Chen Y]] |
| - | [[Category: Lewandowski, E M]] | + | [[Category: Lewandowski EM]] |
| - | [[Category: Smith, E W]] | + | [[Category: Smith EW]] |
| - | [[Category: Chemokine]]
| + | |
| - | [[Category: Chemotaxis]]
| + | |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Inflammation]]
| + | |
| Structural highlights
Function
CCL21_HUMAN Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Shows preferential activity towards naive T-cells. May play a role in mediating homing of lymphocytes to secondary lymphoid organs. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4.
Publication Abstract from PubMed
CCL21 chemokine binds the G protein-coupled receptor CCR7, aiding not only in immune response but also in cancer metastasis. Compared with other chemokines, CCL21 has a unique extended unstructured C-terminus that is truncated in some naturally occurring variants. We have solved the X-ray crystallographic structure of a truncated CCL21 (residues 1-79) lacking the extended C-terminus, and identified, via 2D NMR, a putative sulfotyrosine-binding site that may recognize such post-translationally modified tyrosine residues on the receptor. Compared to the previously solved NMR structure of full-length CCL21, the crystal structure presents new druggable binding hot spots resulting from an alternative N-loop conformation. In addition, whereas the previous NMR structure did not provide any structural information after residue 70, the C-terminus of the truncated CCL21, ordered up to Ala77 in our crystal structure, is placed near the N-loop and sulfotyrosine-binding site, indicating that the extended C-terminus of the full length CCL21 can interact with this important region for receptor binding. These observations suggest a potential origin for the auto-inhibition of CCL21 activity that was recently described. The new crystal structure and binding hot spot analysis have important implications for the function of the CCL21 C-terminus and drug discovery.
Crystallographic structure of truncated CCL21 and putative sulfotyrosine-binding site.,Smith EW, Lewandowski EM, Moussouras NA, Kroeck KG, Volkman BF, Veldkamp CT, Chen Y Biochemistry. 2016 Sep 12. PMID:27617343[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Smith EW, Lewandowski EM, Moussouras NA, Kroeck KG, Volkman BF, Veldkamp CT, Chen Y. Crystallographic structure of truncated CCL21 and putative sulfotyrosine-binding site. Biochemistry. 2016 Sep 12. PMID:27617343 doi:http://dx.doi.org/10.1021/acs.biochem.6b00304
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