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2vxw

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Revision as of 03:35, 25 December 2014

Structural and Functional Studies of the Potent Anti-HIV Chemokine Variant P2-RANTES

Structural highlights

2vxw is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1u4p, 1u4r, 1hrj, 1u4m, 1rto, 1eqt, 1u4l, 1b3a, 1rtn
Resources:	FirstGlance, OCA, RCSB, PDBsum

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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The N-terminal region of the chemokine RANTES is critical for its function. A synthesized N-terminally modified analog of RANTES, P2-RANTES, was discovered using a phage display selection against living CCR5-expressing cells, and has been reported to inhibit HIV-1 env-mediated cell-cell fusion at subnanomolar levels (Hartley et al. J Virol 2003;77:6637-6644). In the present study we produced this protein using E. coli overexpression and extensively studied its structure and function. The x-ray crystal structure of P2-RANTES was solved and refined at 1.7 A resolution. This protein was found to be predominantly a monomer in solution by analytical ultracentrifugation, but a tetramer in the crystal. In studies of glycosaminoglycan binding, P2-RANTES was found to be significantly less able to bind heparin than wild type RANTES. We also tested this protein for receptor internalization where it was shown to be functional, in cell-cell fusion assays where recombinant P2-RANTES was a potent fusion inhibitor (IC(50) = 2.4 +/- 0.8 nM), and in single round infection assays where P2-RANTES inhibited at subnanomolar levels. Further, in a modified fusion assay designed to test specificity of inhibition, P2-RANTES was also highly effective, with a 65-fold improvement over the fusion inhibitor C37, which is closely related to the clinically approved inhibitor T-20. These studies provide detailed structural and functional information for this novel N-terminally modified chemokine mutant. This information will be very useful in the development of more potent anti-HIV agents. PDB Accession Number: 2vxw. Proteins 2009. (c) 2009 Wiley-Liss, Inc.

Structural and functional studies of the potent anti-HIV chemokine variant P2-RANTES.,Jin H, Kagiampakis I, Li P, Liwang PJ Proteins. 2009 Jul 20. PMID:19722264^[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
↑ Jin H, Kagiampakis I, Li P, Liwang PJ. Structural and functional studies of the potent anti-HIV chemokine variant P2-RANTES. Proteins. 2009 Jul 20. PMID:19722264 doi:10.1002/prot.22542

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2vxw"

@@ Line 6: / Line 6: @@
 <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=2vxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vxw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2vxw RCSB], [http://www.ebi.ac.uk/pdbsum/2vxw PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 29: / Line 31: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Jin, H.]]
+[[Category: Jin, H]]
-[[Category: Li, P.]]
+[[Category: Li, P]]
-[[Category: Liwang, P J.]]
+[[Category: Liwang, P J]]
 [[Category: Cell-cell fusion]]
 [[Category: Chemotaxis]]

2vxw

From Proteopedia

Revision as of 03:35, 25 December 2014

Structural and Functional Studies of the Potent Anti-HIV Chemokine Variant P2-RANTES

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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