View source for 8db4


==Crystal structure of the peanut allergen Ara h 2 bound by two neutralizing antibodies 22S1 and 13T1==
<StructureSection load='8db4' size='340' side='right'caption='[[8db4]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8db4]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Arachis_hypogaea Arachis hypogaea] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DB4 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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8db4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8db4 OCA], [https://pdbe.org/8db4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8db4 RCSB], [https://www.ebi.ac.uk/pdbsum/8db4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8db4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A445BYI5_ARAHY A0A445BYI5_ARAHY] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In IgE-mediated food allergies, exposure to the allergen activates systemic allergic responses. Oral immunotherapy (OIT) treats food allergies through incremental increases in oral allergen exposure. However, OIT only induces sustained clinical tolerance and decreased basophil sensitivity in a subset of individuals despite increases in circulating allergen-specific IgG in all treated individuals. Therefore, we examined the allergen-specific antibodies from 2 OIT cohorts of patients with sustained and transient responses. Here, we compared antibodies from individuals with sustained or transient responses and discovered specific tolerance-associated conformational epitopes of the immunodominant allergen Ara h 2 recognized by neutralizing antibodies. First, we identified what we believe to be previously unknown conformational, intrahelical epitopes using x-ray crystallography with recombinant antibodies. We then identified epitopes only recognized in sustained tolerance. Finally, antibodies recognizing tolerance-associated epitopes effectively neutralized allergen to suppress IgE-mediated effector cell activation. Our results demonstrate the molecular basis of antibody-mediated protection in IgE-mediated food allergy, by defining how these antibodies disrupt IgE-allergen interactions to prevent allergic reactions. Our approach to studying the structural and functional basis for neutralizing antibodies demonstrates the clinical relevance of specific antibody clones in antibody-mediated tolerance. We anticipate that our findings will form the foundation for treatments of peanut allergy using neutralizing antibodies and hypoallergens.

Immunotherapy-induced neutralizing antibodies disrupt allergen binding and sustain allergen tolerance in peanut allergy.,LaHood NA, Min J, Keswani T, Richardson CM, Amoako K, Zhou J, Marini-Rapoport O, Bernard H, Hazebrouck S, Shreffler WG, Love JC, Pomes A, Pedersen LC, Mueller GA, Patil SU J Clin Invest. 2023 Jan 17;133(2):e164501. doi: 10.1172/JCI164501. PMID:36647835<ref>PMID:36647835</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8db4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Arachis hypogaea]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Min J]]
[[Category: Pedersen LC]]