1je4

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[[Image:1je4.jpg|left|200px]]
 
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==Solution structure of the monomeric variant of the chemokine MIP-1beta==
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The line below this paragraph, containing "STRUCTURE_1je4", creates the "Structure Box" on the page.
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<StructureSection load='1je4' size='340' side='right'caption='[[1je4]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1je4]] is a 1 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=1JE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JE4 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1je4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1je4 OCA], [https://pdbe.org/1je4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1je4 RCSB], [https://www.ebi.ac.uk/pdbsum/1je4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1je4 ProSAT]</span></td></tr>
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{{STRUCTURE_1je4| PDB=1je4 | SCENE= }}
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</table>
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== Function ==
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'''Solution structure of the monomeric variant of the chemokine MIP-1beta'''
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[https://www.uniprot.org/uniprot/CCL4_HUMAN 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.<ref>PMID:8525373</ref> <ref>PMID:10540332</ref> <ref>PMID:12070155</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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==Overview==
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Check<jmol>
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MIP-1beta, a member of the chemokine family of proteins, tightly binds the receptor CCR5 as part of its natural function in the immune response, and in doing so also blocks the ability of many strains of HIV to enter the cell. The single most important MIP-1beta residue known to contribute to its interaction with the receptor is Phe13, which when mutated reduces the ability of MIP-1beta to bind to CCR5 by more than 1000-fold. To obtain a structural understanding of the dramatic effect of the absence of Phe13 in MIP-1beta, we used multidimensional heteronuclear NMR to determine the three-dimensional structure of the MIP-1beta F13A variant. We had previously shown that, unlike the wild-type protein which has been shown to be a tight dimer, the F13A mutant is monomeric even at high concentrations [Laurence, J. S., Blanpain, C., Burgner, J. W., Parmentier, M., and LiWang, P. J. (2000) Biochemistry 39, 3401-3409], leading to significant changes in the NMR spectra of F13A and the wild-type protein. We have obtained a total of 940 structural restraints for MIP-1beta F13A, and have calculated a family of structures having a backbone rmsd from the average of 0.55 A (residues 12-67). A structural comparison of the F13A mutant with a fully active monomeric variant, P8A, shows that despite some differences in the (1)H-(15)N HSQC spectra the two are nearly identical in NOE distance restraints and in backbone conformation. A comparison of F13A with the wild-type protein shows largely the same fold, although differences exist in the N-terminal and loop regions for which the loss of the dimer in F13A can mainly account. A dynamics comparison confirms greater flexibility in F13A than in the wild-type protein in regions of dimer contact in the wild-type protein. In an analysis to determine if the large functional effect resulting from the loss of Phe13 is due to the local side chain change or due to more global structural changes, we conclude that local effects predominate. This suggests that a strategy for designing tight binding anti-CCR5 therapeutics should include a Phe-like component.
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/je/1je4_consurf.spt"</scriptWhenChecked>
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==About this Structure==
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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1JE4 is a [[Single protein]] structure of 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=1JE4 OCA].
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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==Reference==
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</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=1je4 ConSurf].
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Structural comparison of monomeric variants of the chemokine MIP-1beta having differing ability to bind the receptor CCR5., Kim S, Jao S, Laurence JS, LiWang PJ, Biochemistry. 2001 Sep 11;40(36):10782-91. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11535053 11535053]
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Jao, S.]]
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[[Category: Jao S]]
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[[Category: Kim, S.]]
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[[Category: Kim S]]
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[[Category: Laurence, J S.]]
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[[Category: Laurence JS]]
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[[Category: LiWang, P J.]]
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[[Category: LiWang PJ]]
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[[Category: Chemokine]]
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[[Category: Macrophage inflammatory protein]]
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[[Category: Mip-1beta]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 21:06:43 2008''
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Current revision

Solution structure of the monomeric variant of the chemokine MIP-1beta

PDB ID 1je4

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