View source for 1b50


==NMR STRUCTURE OF HUMAN MIP-1A D26A, 10 STRUCTURES==
<StructureSection load='1b50' size='340' side='right'caption='[[1b50]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1b50]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1B50 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 10 models</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1b50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b50 OCA], [https://pdbe.org/1b50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1b50 RCSB], [https://www.ebi.ac.uk/pdbsum/1b50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1b50 ProSAT]</span></td></tr>
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== Function ==
[https://www.uniprot.org/uniprot/CCL3_HUMAN 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).<ref>PMID:8525373</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b5/1b50_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1b50 ConSurf].
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== Publication Abstract from PubMed ==
Human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation normal T cell expressed) self-associate to form high-molecular mass aggregates. To explore the biological significance of chemokine aggregation, nonaggregating variants were sought. The phenotypes of 105 hMIP-1alpha variants generated by systematic mutagenesis and expression in yeast were determined. hMIP-1alpha residues Asp26 and Glu66 were critical to the self-association process. Substitution at either residue resulted in the formation of essentially homogenous tetramers at 0.5 mg/ml. Substitution of identical or analogous residues in homologous positions in both hMIP-1beta and RANTES demonstrated that they were also critical to aggregation. Our analysis suggests that a single charged residue at either position 26 or 66 is insufficient to support extensive aggregation and that two charged residues must be present. Solution of the three-dimensional NMR structure of hMIP-1alpha has enabled comparison of these residues in hMIP-1beta and RANTES. Aggregated and disaggregated forms of hMIP-1alpha, hMIP-1beta, and RANTES generally have equivalent G-protein-coupled receptor-mediated biological potencies. We have therefore generated novel reagents to evaluate the role of hMIP-1alpha, hMIP-1beta, and RANTES aggregation in vitro and in vivo. The disaggregated chemokines retained their human immunodeficiency virus (HIV) inhibitory activities. Surprisingly, high concentrations of RANTES, but not disaggregated RANTES variants, enhanced infection of cells by both M- and T-tropic HIV isolates/strains. This observation has important implications for potential therapeutic uses of chemokines implying that disaggregated forms may be necessary for safe clinical investigation.

Identification of amino acid residues critical for aggregation of human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES. Characterization of active disaggregated chemokine variants.,Czaplewski LG, McKeating J, Craven CJ, Higgins LD, Appay V, Brown A, Dudgeon T, Howard LA, Meyers T, Owen J, Palan SR, Tan P, Wilson G, Woods NR, Heyworth CM, Lord BI, Brotherton D, Christison R, Craig S, Cribbes S, Edwards RM, Evans SJ, Gilbert R, Morgan P, Randle E, Schofield N, Varley PG, Fisher J, Waltho JP, Hunter MG J Biol Chem. 1999 Jun 4;274(23):16077-84. PMID:10347159<ref>PMID:10347159</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Craven CJ]]
[[Category: Dudgeon T]]
[[Category: Higgins LD]]
[[Category: Tan P]]
[[Category: Waltho JP]]