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2q8r

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Revision as of 12:49, 11 September 2015

Structural and Functional Characterization of CC Chemokine CCL14

Structural highlights

2q8r 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:	2q8t
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[CCL14_HUMAN] Has weak activities on human monocytes and acts via receptors that also recognize MIP-1 alpha. It induced intracellular Ca(2+) changes and enzyme release, but no chemotaxis, at concentrations of 100-1,000 nM, and was inactive on T-lymphocytes, neutrophils, and eosinophil leukocytes. Enhances the proliferation of CD34 myeloid progenitor cells. The processed form HCC-1(9-74) is a chemotactic factor that attracts monocytes eosinophils, and T-cells and is a ligand for CCR1, CCR3 and CCR5.^[1]

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

CC chemokine ligand 14, CCL14, is a human CC chemokine that is of recent interest because of its natural ability, upon proteolytic processing of the first eight NH2-terminal residues, to bind to and signal through the human immunodeficiency virus type-1 (HIV-1) co-receptor, CC chemokine receptor 5 (CCR5). We report X-ray crystallographic structures of both full-length CCL14 and signaling-active, truncated CCL14 [9-74] determined at 2.23 and 1.8 A, respectively. Although CCL14 and CCL14 [9-74] differ in their ability to bind CCR5 for biological signaling, we find that the NH2-terminal eight amino acids (residues 1 through 8) are completely disordered in CCL14 and both show the identical mode of the dimeric assembly characteristic of the CC type chemokine structures. However, analytical ultracentrifugation studies reveal that the CCL14 is stable as a dimer at a concentration as low as 100 nM, whereas CCL14 [9-74] is fully monomeric at the same concentration. By the same method, the equilibrium between monomers of CCL14 [9-74] and higher order oligomers is estimated to be of EC1,4 = 4.98 microM for monomer-tetramer conversion. The relative instability of CCL14 [9-74] oligomers as compared to CCL14 is also reflected in the Kd's that are estimated by the surface plasmon resonance method to be approximately 9.84 and 667 nM for CCL14 and CCL14 [9-74], respectively. This approximately 60-fold difference in stability at a physiologically relevant concentration can potentially account for their different signaling ability. Functional data from the activity assays by intracellular calcium flux and inhibition of CCR5-mediated HIV-1 entry show that only CCL14 [9-74] is fully active at these near-physiological concentrations where CCL14 [9-74] is monomeric and CCL14 is dimeric. These results together suggest that the ability of CCL14 [9-74] to monomerize can play a role for cellular activation.

Structural and functional characterization of CC chemokine CCL14.,Blain KY, Kwiatkowski W, Zhao Q, La Fleur D, Naik C, Chun TW, Tsareva T, Kanakaraj P, Laird MW, Shah R, George L, Sanyal I, Moore PA, Demeler B, Choe S Biochemistry. 2007 Sep 4;46(35):10008-15. Epub 2007 Aug 11. PMID:17691823^[2]

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

References

↑ Detheux M, Standker L, Vakili J, Munch J, Forssmann U, Adermann K, Pohlmann S, Vassart G, Kirchhoff F, Parmentier M, Forssmann WG. Natural proteolytic processing of hemofiltrate CC chemokine 1 generates a potent CC chemokine receptor (CCR)1 and CCR5 agonist with anti-HIV properties. J Exp Med. 2000 Nov 20;192(10):1501-8. PMID:11085751
↑ Blain KY, Kwiatkowski W, Zhao Q, La Fleur D, Naik C, Chun TW, Tsareva T, Kanakaraj P, Laird MW, Shah R, George L, Sanyal I, Moore PA, Demeler B, Choe S. Structural and functional characterization of CC chemokine CCL14. Biochemistry. 2007 Sep 4;46(35):10008-15. Epub 2007 Aug 11. PMID:17691823 doi:10.1021/bi700936w

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/2q8r"

Categories: Homo sapiens | Blain, K Y | Common cc chemokine fold | Cytokine

@@ Line 4: / Line 4: @@
 <table><tr><td colspan='2'>[[2q8r]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q8R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Q8R FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2q8t|2q8t]]</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=2q8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8r OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2q8r RCSB], [http://www.ebi.ac.uk/pdbsum/2q8r PDBsum]</span></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=2q8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8r OCA], [http://pdbe.org/2q8r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2q8r RCSB], [http://www.ebi.ac.uk/pdbsum/2q8r PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 26: / Line 26: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2q8r" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2q8r

From Proteopedia

Revision as of 12:49, 11 September 2015

Structural and Functional Characterization of CC Chemokine CCL14

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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