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5cmd

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Revision as of 11:45, 27 March 2020

Oligomer crystal structure of CC chemokine 5 (CCL5)

Structural highlights

5cmd is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5cor, 5coy, 5d65, 5dnf
Gene:	CCL5, D17S136E, SCYA5 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CCL5_HUMAN] Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. Binds to CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second processed form RANTES(4-68) exhibits reduced chemotactic and HIV-suppressive activity compared with RANTES(1-68) and RANTES(3-68) and is generated by an unidentified enzyme associated with monocytes and neutrophils.^[1] ^[2] ^[3] ^[4] ^[5]

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Capoulade-Metay C, Ayouba A, Kfutwah A, Lole K, Petres S, Dudoit Y, Deterre P, Menu E, Barre-Sinoussi F, Debre P, Theodorou I. A natural CCL5/RANTES variant antagonist for CCR1 and CCR3. Immunogenetics. 2006 Jul;58(7):533-41. Epub 2006 Jun 22. PMID:16791620 doi:http://dx.doi.org/10.1007/s00251-006-0133-2
↑ Kameyoshi Y, Dorschner A, Mallet AI, Christophers E, Schroder JM. Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils. J Exp Med. 1992 Aug 1;176(2):587-92. PMID:1380064
↑ 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
↑ Proost P, De Meester I, Schols D, Struyf S, Lambeir AM, Wuyts A, Opdenakker G, De Clercq E, Scharpe S, Van Damme J. Amino-terminal truncation of chemokines by CD26/dipeptidyl-peptidase IV. Conversion of RANTES into a potent inhibitor of monocyte chemotaxis and HIV-1-infection. J Biol Chem. 1998 Mar 27;273(13):7222-7. PMID:9516414
↑ Lim JK, Burns JM, Lu W, DeVico AL. Multiple pathways of amino terminal processing produce two truncated variants of RANTES/CCL5. J Leukoc Biol. 2005 Aug;78(2):442-52. Epub 2005 May 27. PMID:15923218 doi:http://dx.doi.org/jlb.0305161
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5cmd"

@@ Line 1: / Line 1: @@
 ==Oligomer crystal structure of CC chemokine 5 (CCL5)==
-<StructureSection load='5cmd' size='340' side='right' caption='[[5cmd]], [[Resolution|resolution]] 3.09&Aring;' scene=''>
+<StructureSection load='5cmd' size='340' side='right'caption='[[5cmd]], [[Resolution|resolution]] 3.09&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5cmd]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CMD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5cmd]] 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=5CMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CMD 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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cor|5cor]], [[5coy|5coy]], [[5d65|5d65]], [[5dnf|5dnf]]</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=5cmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cmd OCA], [http://pdbe.org/5cmd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cmd RCSB], [http://www.ebi.ac.uk/pdbsum/5cmd PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCL5, D17S136E, SCYA5 ([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=5cmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cmd OCA], [http://pdbe.org/5cmd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cmd RCSB], [http://www.ebi.ac.uk/pdbsum/5cmd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cmd ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Liang, W G]]
 [[Category: Tang, W J]]

5cmd

From Proteopedia

Revision as of 11:45, 27 March 2020

Oligomer crystal structure of CC chemokine 5 (CCL5)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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