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==Oligomeric Structure of the Chemokine CCL5/RANTES from NMR, MS, and SAXS Data==
==Oligomeric Structure of the Chemokine CCL5/RANTES from NMR, MS, and SAXS Data==
<StructureSection load='2l9h' size='340' side='right'caption='[[2l9h]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
<StructureSection load='2l9h' size='340' side='right'caption='[[2l9h]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2l9h]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L9H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L9H FirstGlance]. <br>
<table><tr><td colspan='2'>[[2l9h]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L9H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L9H FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1u4l|1u4l]]</div></td></tr>
</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=2l9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l9h OCA], [https://pdbe.org/2l9h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l9h RCSB], [https://www.ebi.ac.uk/pdbsum/2l9h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l9h ProSAT]</span></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCL5, D17S136E, SCYA5 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2l9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l9h OCA], [https://pdbe.org/2l9h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l9h RCSB], [https://www.ebi.ac.uk/pdbsum/2l9h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l9h ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/CCL5_HUMAN 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.<ref>PMID:16791620</ref> <ref>PMID:1380064</ref> <ref>PMID:8525373</ref> <ref>PMID:9516414</ref> <ref>PMID:15923218</ref>
[https://www.uniprot.org/uniprot/CCL5_HUMAN 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.<ref>PMID:16791620</ref> <ref>PMID:1380064</ref> <ref>PMID:8525373</ref> <ref>PMID:9516414</ref> <ref>PMID:15923218</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: Handel, T M]]
[[Category: Handel TM]]
[[Category: Prestegard, J H]]
[[Category: Prestegard JH]]
[[Category: Sharp, J S]]
[[Category: Sharp JS]]
[[Category: Wang, X]]
[[Category: Wang X]]
[[Category: Watson, C M]]
[[Category: Watson CM]]
[[Category: Chemokine]]
[[Category: Immune system]]
[[Category: Oligomer]]

Revision as of 11:27, 18 January 2023

Oligomeric Structure of the Chemokine CCL5/RANTES from NMR, MS, and SAXS DataOligomeric Structure of the Chemokine CCL5/RANTES from NMR, MS, and SAXS Data

Structural highlights

2l9h is a 4 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
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

CCL5 (RANTES) is a proinflammatory chemokine known to activate leukocytes through its receptor, CCR5. Although the monomeric form of CCL5 is sufficient to cause cell migration in vitro, CCL5's propensity for aggregation is essential for migration in vivo, T cell activation and apoptosis, and HIV entry into cells. However, there is currently no structural information on CCL5 oligomers larger than the canonical CC chemokine dimer. In this study the solution structure of a CCL5 oligomer was investigated using an integrated approach, including NMR residual dipolar couplings to determine allowed relative orientations of the component monomers, SAXS to restrict overall shape, and hydroxyl radical footprinting and NMR cross-saturation experiments to identify interface residues. The resulting model of the CCL5 oligomer provides a basis for explaining the disaggregating effect of E66 and E26 mutations and suggests mechanisms by which glycosaminoglycan binding may promote oligomer formation and facilitate cell migration in vivo.

Oligomeric Structure of the Chemokine CCL5/RANTES from NMR, MS, and SAXS Data.,Wang X, Watson C, Sharp JS, Handel TM, Prestegard JH Structure. 2011 Aug 10;19(8):1138-48. PMID:21827949[6]

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

References

  1. 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
  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
  3. 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
  4. 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
  5. 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
  6. Wang X, Watson C, Sharp JS, Handel TM, Prestegard JH. Oligomeric Structure of the Chemokine CCL5/RANTES from NMR, MS, and SAXS Data. Structure. 2011 Aug 10;19(8):1138-48. PMID:21827949 doi:10.1016/j.str.2011.06.001
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