2x6l

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(Difference between revisions)

Revision as of 11:22, 5 August 2016

X-RAY STRUCTURE OF MACROPHAGE INFLAMMATORY PROTEIN-1 BETA

Structural highlights

2x6l is a 5 chain structure. This structure supersedes the now removed PDB entry 3kkh. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1hum, 1je4, 1hun, 2x6g
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CCL4_HUMAN] Monokine with inflammatory and chemokinetic properties. Binds to CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-beta induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form MIP-1-beta(3-69) retains the abilities to induce down-modulation of surface expression of the chemokine receptor CCR5 and to inhibit the CCR5-mediated entry of HIV-1 in T-cells. MIP-1-beta(3-69) is also a ligand for CCR1 and CCR2 isoform B.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Macrophage inflammatory protein-1 (MIP-1), MIP-1alpha (CCL3) and MIP-1beta (CCL4) are chemokines crucial for immune responses towards infection and inflammation. Both MIP-1alpha and MIP-1beta form high-molecular-weight aggregates. Our crystal structures reveal that MIP-1 aggregation is a polymerization process and human MIP-1alpha and MIP-1beta form rod-shaped, double-helical polymers. Biophysical analyses and mathematical modelling show that MIP-1 reversibly forms a polydisperse distribution of rod-shaped polymers in solution. Polymerization buries receptor-binding sites of MIP-1alpha, thus depolymerization mutations enhance MIP-1alpha to arrest monocytes onto activated human endothelium. However, same depolymerization mutations render MIP-1alpha ineffective in mouse peritoneal cell recruitment. Mathematical modelling reveals that, for a long-range chemotaxis of MIP-1, polymerization could protect MIP-1 from proteases that selectively degrade monomeric MIP-1. Insulin-degrading enzyme (IDE) is identified as such a protease and decreased expression of IDE leads to elevated MIP-1 levels in microglial cells. Our structural and proteomic studies offer a molecular basis for selective degradation of MIP-1. The regulated MIP-1 polymerization and selective inactivation of MIP-1 monomers by IDE could aid in controlling the MIP-1 chemotactic gradient for immune surveillance.

Polymerization of MIP-1 chemokine (CCL3 and CCL4) and clearance of MIP-1 by insulin-degrading enzyme.,Ren M, Guo Q, Guo L, Lenz M, Qian F, Koenen RR, Xu H, Schilling AB, Weber C, Ye RD, Dinner AR, Tang WJ EMBO J. 2010 Oct 19. PMID:20959807^[4]

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
↑ Garlisi CG, Xiao H, Tian F, Hedrick JA, Billah MM, Egan RW, Umland SP. The assignment of chemokine-chemokine receptor pairs: TARC and MIP-1 beta are not ligands for human CC-chemokine receptor 8. Eur J Immunol. 1999 Oct;29(10):3210-5. PMID:10540332 doi:http://dx.doi.org/10.1002/(SICI)1521-4141(199910)29:10<3210::AID-IMMU3210>3.0.CO;2-W
↑ Guan E, Wang J, Roderiquez G, Norcross MA. Natural truncation of the chemokine MIP-1 beta /CCL4 affects receptor specificity but not anti-HIV-1 activity. J Biol Chem. 2002 Aug 30;277(35):32348-52. Epub 2002 Jun 17. PMID:12070155 doi:http://dx.doi.org/10.1074/jbc.M203077200
↑ Ren M, Guo Q, Guo L, Lenz M, Qian F, Koenen RR, Xu H, Schilling AB, Weber C, Ye RD, Dinner AR, Tang WJ. Polymerization of MIP-1 chemokine (CCL3 and CCL4) and clearance of MIP-1 by insulin-degrading enzyme. EMBO J. 2010 Oct 19. PMID:20959807 doi:10.1038/emboj.2010.256

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/2x6l"

@@ Line 1: / Line 1: @@
 ==X-RAY STRUCTURE OF MACROPHAGE INFLAMMATORY PROTEIN-1 BETA==
 <StructureSection load='2x6l' size='340' side='right' caption='[[2x6l]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hum|1hum]], [[1je4|1je4]], [[1hun|1hun]], [[2x6g|2x6g]]</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=2x6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x6l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2x6l RCSB], [http://www.ebi.ac.uk/pdbsum/2x6l 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=2x6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x6l OCA], [http://pdbe.org/2x6l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2x6l RCSB], [http://www.ebi.ac.uk/pdbsum/2x6l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2x6l ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2x6l" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2x6l

From Proteopedia

Revision as of 11:22, 5 August 2016

X-RAY STRUCTURE OF MACROPHAGE INFLAMMATORY PROTEIN-1 BETA

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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