4ra8

From Proteopedia

(Difference between revisions)

Revision as of 17:27, 9 March 2017

Structure analysis of the Mip1a P8A mutant

Structural highlights

4ra8 is a 5 chain structure. This structure supersedes the now removed PDB entry 3tn1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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

CC chemokine ligands (CCLs) are 8- to 14-kDa signaling proteins involved in diverse immune functions. While CCLs share similar tertiary structures, oligomerization produces highly diverse quaternary structures that protect chemokines from proteolytic degradation and modulate their functions. CCL18 is closely related to CCL3 and CCL4 with respect to both protein sequence and genomic location, yet CCL18 has distinct biochemical and biophysical properties. Here, we report a crystal structure of human CCL18 and its oligomerization states in solution based on crystallographic and small-angle X-ray scattering analyses. Our data show that CCL18 adopts an alpha-helical conformation at its N-terminus that weakens its dimerization, explaining CCL18's preference for the monomeric state. Multiple contacts between monomers allow CCL18 to reversibly form a unique open-ended oligomer different from those of CCL3, CCL4, and CCL5. Furthermore, these differences hinge on proline 8, which is conserved in CCL3 and CCL4 but is replaced by lysine in human CCL18. Our structural analyses suggest that a mutation of proline 8 to alanine stabilizes a type 1 beta-turn at the N-terminus of CCL4 to prevent dimerization but prevents dimers from making key contacts with each other in CCL3. Thus, the P8A mutation induces depolymerization of CCL3 and CCL4 by distinct mechanisms. Finally, we used structural, biochemical, and functional analyses to unravel why insulin-degrading enzyme degrades CCL3 and CCL4 but not CCL18. Our results elucidate the molecular basis for the oligomerization of three closely related CC chemokines and suggest how oligomerization shapes CCL chemokine function.

Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme.,Liang WG, Ren M, Zhao F, Tang WJ J Mol Biol. 2015 Mar 27;427(6 Pt B):1345-58. doi: 10.1016/j.jmb.2015.01.012. Epub, 2015 Jan 28. PMID:25636406^[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
↑ Liang WG, Ren M, Zhao F, Tang WJ. Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme. J Mol Biol. 2015 Mar 27;427(6 Pt B):1345-58. doi: 10.1016/j.jmb.2015.01.012. Epub, 2015 Jan 28. PMID:25636406 doi:http://dx.doi.org/10.1016/j.jmb.2015.01.012

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/4ra8"

Categories: Guo, Q | Liang, W G | Ren, M | Tang, W J | Cytokine

@@ Line 1: / Line 1: @@
 ==Structure analysis of the Mip1a P8A mutant==
 <StructureSection load='4ra8' size='340' side='right' caption='[[4ra8]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4ra8]] is a 5 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3tn1 3tn1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RA8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RA8 FirstGlance]. <br>
-</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=4ra8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ra8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ra8 RCSB], [http://www.ebi.ac.uk/pdbsum/4ra8 PDBsum]</span></td></tr>
+</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=4ra8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ra8 OCA], [http://pdbe.org/4ra8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ra8 RCSB], [http://www.ebi.ac.uk/pdbsum/4ra8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ra8 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 15: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4ra8" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4ra8

From Proteopedia

Revision as of 17:27, 9 March 2017

Structure analysis of the Mip1a P8A mutant

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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