2bc4

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(New page: 200px<br /><applet load="2bc4" size="450" color="white" frame="true" align="right" spinBox="true" caption="2bc4, resolution 2.270&Aring;" /> '''Crystal structure o...)
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[[Image:2bc4.gif|left|200px]]<br /><applet load="2bc4" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2bc4, resolution 2.270&Aring;" />
 
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'''Crystal structure of HLA-DM'''<br />
 
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==Overview==
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==Crystal structure of HLA-DM==
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HLA-DM (DM) plays a critical role in Ag presentation to CD4 T cells by, catalyzing the exchange of peptides bound to MHC class II molecules. Large, lateral surfaces involved in the DM:HLA-DR (DR) interaction have been, defined, but the mechanism of catalysis is not understood. In this study, we describe four small molecules that accelerate DM-catalyzed peptide, exchange. Mechanistic studies demonstrate that these small molecules, substantially enhance the catalytic efficiency of DM, indicating that they, make the transition state of the DM:DR/peptide complex energetically more, favorable. These compounds fall into two functional classes: two compounds, are active only in the presence of DM, and binding data for one show a, direct interaction with DM. The remaining two compounds have partial, activity in the absence of DM, suggesting that they may act at the, interface between DM and DR/peptide. A hydrophobic ridge in the DMbeta1, domain was implicated in the catalysis of peptide exchange because the, activity of three of these enhancers was substantially reduced by point, mutations in this area.
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<StructureSection load='2bc4' size='340' side='right'caption='[[2bc4]], [[Resolution|resolution]] 2.27&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2bc4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BC4 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.27&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene></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=2bc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bc4 OCA], [https://pdbe.org/2bc4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bc4 RCSB], [https://www.ebi.ac.uk/pdbsum/2bc4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bc4 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/DMA_HUMAN DMA_HUMAN] Plays a critical role in catalyzing the release of class II-associated invariant chain peptide (CLIP) from newly synthesized MHC class II molecules and freeing the peptide binding site for acquisition of antigenic peptides. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO.<ref>PMID:8849454</ref> <ref>PMID:9768757</ref> <ref>PMID:16547258</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bc/2bc4_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=2bc4 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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HLA-DM (DM) plays a critical role in Ag presentation to CD4 T cells by catalyzing the exchange of peptides bound to MHC class II molecules. Large lateral surfaces involved in the DM:HLA-DR (DR) interaction have been defined, but the mechanism of catalysis is not understood. In this study, we describe four small molecules that accelerate DM-catalyzed peptide exchange. Mechanistic studies demonstrate that these small molecules substantially enhance the catalytic efficiency of DM, indicating that they make the transition state of the DM:DR/peptide complex energetically more favorable. These compounds fall into two functional classes: two compounds are active only in the presence of DM, and binding data for one show a direct interaction with DM. The remaining two compounds have partial activity in the absence of DM, suggesting that they may act at the interface between DM and DR/peptide. A hydrophobic ridge in the DMbeta1 domain was implicated in the catalysis of peptide exchange because the activity of three of these enhancers was substantially reduced by point mutations in this area.
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==About this Structure==
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Small molecules that enhance the catalytic efficiency of HLA-DM.,Nicholson MJ, Moradi B, Seth NP, Xing X, Cuny GD, Stein RL, Wucherpfennig KW J Immunol. 2006 Apr 1;176(7):4208-20. PMID:16547258<ref>PMID:16547258</ref>
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2BC4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BC4 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Small molecules that enhance the catalytic efficiency of HLA-DM., Nicholson MJ, Moradi B, Seth NP, Xing X, Cuny GD, Stein RL, Wucherpfennig KW, J Immunol. 2006 Apr 1;176(7):4208-20. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16547258 16547258]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 2bc4" style="background-color:#fffaf0;"></div>
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[[Category: Protein complex]]
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[[Category: Cuny, G.D.]]
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[[Category: Moradi, B.]]
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[[Category: Nicholson, M.J.]]
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[[Category: Seth, N.P.]]
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[[Category: Stein, R.L.]]
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[[Category: Wucherpfennig, K.W.]]
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[[Category: Xing, X.]]
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[[Category: CL]]
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[[Category: mhc class ii]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 08:42:52 2007''
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==See Also==
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*[[MHC 3D structures|MHC 3D structures]]
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*[[MHC II 3D structures|MHC II 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Cuny GD]]
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[[Category: Moradi B]]
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[[Category: Nicholson MJ]]
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[[Category: Seth NP]]
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[[Category: Stein RL]]
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[[Category: Wucherpfennig KW]]
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[[Category: Xing X]]

Current revision

Crystal structure of HLA-DM

PDB ID 2bc4

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