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| | ==X-RAY STRUCTURE OF MACROPHAGE INFLAMMATORY PROTEIN-1 ALPHA (CCL3) WITH HEPARIN COMPLEX== | | ==X-RAY STRUCTURE OF MACROPHAGE INFLAMMATORY PROTEIN-1 ALPHA (CCL3) WITH HEPARIN COMPLEX== |
| - | <StructureSection load='5d65' size='340' side='right' caption='[[5d65]], [[Resolution|resolution]] 3.10Å' scene=''> | + | <StructureSection load='5d65' size='340' side='right'caption='[[5d65]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5d65]] is a 5 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=5D65 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D65 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5d65]] is a 5 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=5D65 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5D65 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=IDS:2-O-SULFO-ALPHA-L-IDOPYRANURONIC+ACID'>IDS</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=IDS:2-O-SULFO-ALPHA-L-IDOPYRANURONIC+ACID'>IDS</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cor|5cor]], [[5cmd|5cmd]], [[5coy|5coy]], [[5dnf|5dnf]]</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=5d65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d65 OCA], [https://pdbe.org/5d65 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5d65 RCSB], [https://www.ebi.ac.uk/pdbsum/5d65 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5d65 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCL3, G0S19-1, MIP1A, SCYA3 ([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=5d65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d65 OCA], [http://pdbe.org/5d65 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d65 RCSB], [http://www.ebi.ac.uk/pdbsum/5d65 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5d65 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CCL3_HUMAN CCL3_HUMAN]] Monokine with inflammatory and chemokinetic properties. Binds to CCR1, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-alpha induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV).<ref>PMID:8525373</ref> | + | [https://www.uniprot.org/uniprot/CCL3_HUMAN CCL3_HUMAN] Monokine with inflammatory and chemokinetic properties. Binds to CCR1, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-alpha induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV).<ref>PMID:8525373</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: Hung, S C]] | + | [[Category: Large Structures]] |
| - | [[Category: Hwang, D Y]] | + | [[Category: Hung SC]] |
| - | [[Category: Liang, W G]] | + | [[Category: Hwang DY]] |
| - | [[Category: Tang, W]] | + | [[Category: Liang WG]] |
| - | [[Category: Zulueta, M M]] | + | [[Category: Tang W]] |
| - | [[Category: Cc chemokine]] | + | [[Category: Zulueta MM]] |
| - | [[Category: Ccl3]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Gag]]
| + | |
| - | [[Category: Heparin]]
| + | |
| - | [[Category: Oligomer]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
CCL3_HUMAN Monokine with inflammatory and chemokinetic properties. Binds to CCR1, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-alpha induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV).[1]
Publication Abstract from PubMed
CC chemokine ligand 5 (CCL5) and CCL3 are critical for immune surveillance and inflammation. Consequently, they are linked to the pathogenesis of many inflammatory conditions and are therapeutic targets. Oligomerization and glycosaminoglycan (GAG) binding of CCL5 and CCL3 are vital for the functions of these chemokines. Our structural and biophysical analyses of human CCL5 reveal that CCL5 oligomerization is a polymerization process in which CCL5 forms rod-shaped, double-helical oligomers. This CCL5 structure explains mutational data and offers a unified mechanism for CCL3, CCL4, and CCL5 assembly into high-molecular-weight, polydisperse oligomers. A conserved, positively charged BBXB motif is key for the binding of CC chemokines to GAG. However, this motif is partially buried when CCL3, CCL4, and CCL5 are oligomerized; thus, the mechanism by which GAG binds these chemokine oligomers has been elusive. Our structures of GAG-bound CCL5 and CCL3 oligomers reveal that these chemokine oligomers have distinct GAG-binding mechanisms. The CCL5 oligomer uses another positively charged and fully exposed motif, KKWVR, in GAG binding. However, residues from two partially buried BBXB motifs along with other residues combine to form a GAG-binding groove in the CCL3 oligomer. The N termini of CC chemokines are shown to be involved in receptor binding and oligomerization. We also report an alternative CCL3 oligomer structure that reveals how conformational changes in CCL3 N termini profoundly alter its surface properties and dimer-dimer interactions to affect GAG binding and oligomerization. Such complexity in oligomerization and GAG binding enables intricate, physiologically relevant regulation of CC chemokine functions.
Structural basis for oligomerization and glycosaminoglycan binding of CCL5 and CCL3.,Liang WG, Triandafillou CG, Huang TY, Zulueta MM, Banerjee S, Dinner AR, Hung SC, Tang WJ Proc Natl Acad Sci U S A. 2016 May 3;113(18):5000-5. doi:, 10.1073/pnas.1523981113. Epub 2016 Apr 18. PMID:27091995[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995 Dec 15;270(5243):1811-5. PMID:8525373
- ↑ Liang WG, Triandafillou CG, Huang TY, Zulueta MM, Banerjee S, Dinner AR, Hung SC, Tang WJ. Structural basis for oligomerization and glycosaminoglycan binding of CCL5 and CCL3. Proc Natl Acad Sci U S A. 2016 May 3;113(18):5000-5. doi:, 10.1073/pnas.1523981113. Epub 2016 Apr 18. PMID:27091995 doi:http://dx.doi.org/10.1073/pnas.1523981113
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