1xf2: Difference between revisions

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OCA

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-[[Image:1xf2.gif|left|200px]]<br />
-<applet load="1xf2" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1xf2, resolution 2.30&Aring;" />
-'''Structure of Fab DNA-1 complexed with dT3'''<br />
-==Overview==
+==Structure of Fab DNA-1 complexed with dT3==
-Anti-DNA antibodies play important roles in the pathogenesis of autoimmune, diseases. They also represent a unique and relatively unexplored class of, DNA-binding protein. Here, we present a study of conformational changes, induced by DNA binding to an anti-ssDNA Fab known as DNA-1. Three crystal, structures are reported: a complex of DNA-1 bound to dT3, and two, structures of the ligand-free Fab. One of the ligand-free structures was, determined from crystals exhibiting perfect hemihedral twinning, and the, details of structure determination are provided. Unexpectedly, five, residues (H97-H100A) in the apex of heavy chain, complementarity-determining region 3 (HCDR3) are disordered in both, ligand-free structures. Ligand binding also caused a 2-4A shift of the, backbone of Tyr L92 and ordering of the L92 side-chain. In contrast, these, residues are highly ordered in the Fab/dT3 complex, where Tyr H100 and Tyr, H100A form intimate stacking interactions with DNA bases, and L92 forms, the 5' end of the binding site. The structures suggest that HCDR3 is very, flexible and adopts multiple conformations in the ligand-free state. These, results are discussed in terms of induced fit and pre-existing equilibrium, theories of ligand binding. Our results allow new interpretations of, existing thermodynamic and mutagenesis data in terms of conformational, entropy and the volume of conformational space accessible to HCDR3 in the, ligand-free state. In the context of autoimmune disease, plasticity of the, ligand-free antibody could provide a mechanism by which anti-DNA, antibodies bind diverse host ligands, and thereby contribute to, pathogenicity.
+<StructureSection load='1xf2' size='340' side='right'caption='[[1xf2]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1xf2]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XF2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XF2 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=1xf2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xf2 OCA], [https://pdbe.org/1xf2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xf2 RCSB], [https://www.ebi.ac.uk/pdbsum/1xf2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xf2 ProSAT]</span></td></tr>
+</table>
+== 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/xf/1xf2_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=1xf2 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Anti-DNA antibodies play important roles in the pathogenesis of autoimmune diseases. They also represent a unique and relatively unexplored class of DNA-binding protein. Here, we present a study of conformational changes induced by DNA binding to an anti-ssDNA Fab known as DNA-1. Three crystal structures are reported: a complex of DNA-1 bound to dT3, and two structures of the ligand-free Fab. One of the ligand-free structures was determined from crystals exhibiting perfect hemihedral twinning, and the details of structure determination are provided. Unexpectedly, five residues (H97-H100A) in the apex of heavy chain complementarity-determining region 3 (HCDR3) are disordered in both ligand-free structures. Ligand binding also caused a 2-4A shift of the backbone of Tyr L92 and ordering of the L92 side-chain. In contrast, these residues are highly ordered in the Fab/dT3 complex, where Tyr H100 and Tyr H100A form intimate stacking interactions with DNA bases, and L92 forms the 5' end of the binding site. The structures suggest that HCDR3 is very flexible and adopts multiple conformations in the ligand-free state. These results are discussed in terms of induced fit and pre-existing equilibrium theories of ligand binding. Our results allow new interpretations of existing thermodynamic and mutagenesis data in terms of conformational entropy and the volume of conformational space accessible to HCDR3 in the ligand-free state. In the context of autoimmune disease, plasticity of the ligand-free antibody could provide a mechanism by which anti-DNA antibodies bind diverse host ligands, and thereby contribute to pathogenicity.
-==About this Structure==
+Evidence for structural plasticity of heavy chain complementarity-determining region 3 in antibody-ssDNA recognition.,Schuermann JP, Prewitt SP, Davies C, Deutscher SL, Tanner JJ J Mol Biol. 2005 Apr 15;347(5):965-78. PMID:15784256<ref>PMID:15784256</ref>
-XF2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XF2 OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Evidence for structural plasticity of heavy chain complementarity-determining region 3 in antibody-ssDNA recognition., Schuermann JP, Prewitt SP, Davies C, Deutscher SL, Tanner JJ, J Mol Biol. 2005 Apr 15;347(5):965-78. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15784256 15784256]
+</div>
+<div class="pdbe-citations 1xf2" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Antibody 3D structures|Antibody 3D structures]]
+*[[3D structures of non-human antibody|3D structures of non-human antibody]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Protein complex]]
+[[Category: Deutscher SL]]
-[[Category: Deutscher, S.L.]]
+[[Category: Prewitt SP]]
-[[Category: Prewitt, S.P.]]
+[[Category: Schuermann JP]]
-[[Category: Schuermann, J.P.]]
+[[Category: Tanner JJ]]
-[[Category: Tanner, J.J.]]
-[[Category: SO4]]
-[[Category: anti-dna]]
-[[Category: anti-ssdna]]
-[[Category: antibody]]
-[[Category: autoantibody]]
-[[Category: fab]]
-[[Category: immunoglobulin]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:44:23 2007''