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New page: left|200px<br /> <applet load="2dbl" size="450" color="white" frame="true" align="right" spinBox="true" caption="2dbl, resolution 2.9Å" /> '''MOLECULAR BASIS OF C... |
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== | ==MOLECULAR BASIS OF CROSS-REACTIVITY AND THE LIMITS OF ANTIBODY-ANTIGEN COMPLEMENTARITY== | ||
Two major unanswered questions concerning the specificity of antibodies | <StructureSection load='2dbl' size='340' side='right'caption='[[2dbl]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2dbl]] is a 2 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=2DBL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DBL 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]] 2.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=S5H:5-ALPHA-PREGNANE-3-BETA-OL-HEMISUCCINATE'>S5H</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=2dbl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dbl OCA], [https://pdbe.org/2dbl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dbl RCSB], [https://www.ebi.ac.uk/pdbsum/2dbl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dbl ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/IGHG1_MOUSE IGHG1_MOUSE] | |||
== 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/db/2dbl_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=2dbl ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Two major unanswered questions concerning the specificity of antibodies are: how do structurally different antigens bind with high affinity to the same antibody, and what are the limits of the antibody combining site complementarity and flexibility that contribute to such crossreactivity? We report here a comparative analysis of the X-ray structures of five conformationally different steroids in complex with the Fab' fragment of an anti-progesterone antibody DB3 at 2.7 A. This antibody is unable to complement completely the shape of the hydrophobic antigen so that crossreactivity occurs with other ligands without major structural rearrangements of the binding site. Antigen specificity can be explained through conserved interactions of DB3 with the steroid D-ring, whereas some of the crossreactivity is realized through different binding orientations of the steroid skeleton that place the A-ring into alternative pockets on the antibody surface. The restricted gene usage of the VGAM3.8 family in the generation of anti-progesterone monoclonal antibodies may be explained by the specific interaction of VH hallmark residues with the steroid D-ring. This first detailed structure of steroid interactions with a protein could be applied to the understanding of general mechanisms of steroid recognition as well as in the design of specific binding sites for small hydrophobic ligands. | |||
Molecular basis of crossreactivity and the limits of antibody-antigen complementarity.,Arevalo JH, Taussig MJ, Wilson IA Nature. 1993 Oct 28;365(6449):859-63. PMID:8413674<ref>PMID:8413674</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2dbl" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Sandbox 20009|Sandbox 20009]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Arevalo JH]] | |||
[[Category: Wilson IA]] | |||
Latest revision as of 10:50, 23 October 2024
MOLECULAR BASIS OF CROSS-REACTIVITY AND THE LIMITS OF ANTIBODY-ANTIGEN COMPLEMENTARITYMOLECULAR BASIS OF CROSS-REACTIVITY AND THE LIMITS OF ANTIBODY-ANTIGEN COMPLEMENTARITY
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedTwo major unanswered questions concerning the specificity of antibodies are: how do structurally different antigens bind with high affinity to the same antibody, and what are the limits of the antibody combining site complementarity and flexibility that contribute to such crossreactivity? We report here a comparative analysis of the X-ray structures of five conformationally different steroids in complex with the Fab' fragment of an anti-progesterone antibody DB3 at 2.7 A. This antibody is unable to complement completely the shape of the hydrophobic antigen so that crossreactivity occurs with other ligands without major structural rearrangements of the binding site. Antigen specificity can be explained through conserved interactions of DB3 with the steroid D-ring, whereas some of the crossreactivity is realized through different binding orientations of the steroid skeleton that place the A-ring into alternative pockets on the antibody surface. The restricted gene usage of the VGAM3.8 family in the generation of anti-progesterone monoclonal antibodies may be explained by the specific interaction of VH hallmark residues with the steroid D-ring. This first detailed structure of steroid interactions with a protein could be applied to the understanding of general mechanisms of steroid recognition as well as in the design of specific binding sites for small hydrophobic ligands. Molecular basis of crossreactivity and the limits of antibody-antigen complementarity.,Arevalo JH, Taussig MJ, Wilson IA Nature. 1993 Oct 28;365(6449):859-63. PMID:8413674[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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