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2x69

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Revision as of 15:05, 8 July 2020

X-ray Structure of Macrophage Inflammatory Protein-1 alpha polymer

Structural highlights

2x69 is a 5 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1b50, 1b53, 2x6g
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CCL3_HUMAN] Monokine with inflammatory and chemokinetic properties. Binds to CCR1, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-alpha induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV).^[1]

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^[2]

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
↑ 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/2x69"

@@ Line 1: / Line 1: @@
 ==X-ray Structure of Macrophage Inflammatory Protein-1 alpha polymer==
-<StructureSection load='2x69' size='340' side='right' caption='[[2x69]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
+<StructureSection load='2x69' size='340' side='right'caption='[[2x69]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2x69]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X69 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2X69 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2x69]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X69 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2X69 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1b50|1b50]], [[1b53|1b53]], [[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=2x69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x69 OCA], [http://pdbe.org/2x69 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2x69 RCSB], [http://www.ebi.ac.uk/pdbsum/2x69 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2x69 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2x69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x69 OCA], [http://pdbe.org/2x69 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2x69 RCSB], [http://www.ebi.ac.uk/pdbsum/2x69 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2x69 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Guo, Q]]
 [[Category: Ren, M]]

2x69

From Proteopedia

Revision as of 15:05, 8 July 2020

X-ray Structure of Macrophage Inflammatory Protein-1 alpha polymer

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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