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==Crystal structure analysis of the anti-arsonate germline antibody 36-65==
==Crystal structure analysis of the anti-arsonate germline antibody 36-65==
<StructureSection load='2a6j' size='340' side='right' caption='[[2a6j]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
<StructureSection load='2a6j' size='340' side='right'caption='[[2a6j]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2a6j]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A6J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2A6J FirstGlance]. <br>
<table><tr><td colspan='2'>[[2a6j]] is a 4 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=2A6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A6J FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2a6i|2a6i]], [[2a6d|2a6d]]</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a6j OCA], [http://pdbe.org/2a6j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2a6j RCSB], [http://www.ebi.ac.uk/pdbsum/2a6j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2a6j ProSAT]</span></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=2a6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a6j OCA], [https://pdbe.org/2a6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a6j RCSB], [https://www.ebi.ac.uk/pdbsum/2a6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a6j ProSAT]</span></td></tr>
</table>
</table>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
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Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a6/2a6j_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a6/2a6j_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
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<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
The limited primary antibody repertoire uses multiple mechanisms to account for the large number of potential antigens. In this issue of Immunity, Sethi et al. (2006) describe a new means for expanding the antibody repertoire, whereby a single antibody isomer binds diverse antigens at different regions of the binding site.
Correlation between the promiscuity of the primary antibody response and conformational flexibility in a germline antibody was addressed by using germline antibody 36-65. Crystallographic analyses of the 36-65 Fab with three independent dodecapeptides provided mechanistic insights into the generation of antibody diversity. While four antigen-free Fab molecules provided a quantitative description of the conformational repertoire of the antibody CDRs, three Fab molecules bound to structurally diverse peptide epitopes exhibited a common paratope conformation. Each peptide revealed spatially different footprints within the antigen-combining site. However, a conformation-specific lock involving two shared residues, which were also associated with hapten binding, was discernible. Unlike the hapten, the peptides interacted with residues that undergo somatic mutations, suggesting a possible mechanism for excluding "nonspecific" antigens during affinity maturation. The observed multiple binding modes of diverse epitopes within a common paratope conformation of a germline antibody reveal a simple, yet elegant, mechanism for expanding the primary antibody repertoire.


Multiple paths to multispecificity.,Mariuzza RA Immunity. 2006 Apr;24(4):359-61. PMID:16618592<ref>PMID:16618592</ref>
Differential epitope positioning within the germline antibody paratope enhances promiscuity in the primary immune response.,Sethi DK, Agarwal A, Manivel V, Rao KV, Salunke DM Immunity. 2006 Apr;24(4):429-38. PMID:16618601<ref>PMID:16618601</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
==See Also==
*[[3D structures of antibody|3D structures of antibody]]
*[[Antibody 3D structures|Antibody 3D structures]]
*[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Lk3 transgenic mice]]
[[Category: Large Structures]]
[[Category: Agarwal, A]]
[[Category: Mus musculus]]
[[Category: Manivel, V]]
[[Category: Agarwal A]]
[[Category: Rao, K V]]
[[Category: Manivel V]]
[[Category: Salunke, D M]]
[[Category: Rao KV]]
[[Category: Sethi, D K]]
[[Category: Salunke DM]]
[[Category: Germline]]
[[Category: Sethi DK]]
[[Category: Immune system]]
[[Category: Immunoglobulin fold]]

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