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'''Unreleased structure'''


The entry 9ncd is ON HOLD  until Paper Publication
==Crystal structure of the peanut allergen Ara h 9 with bound Fab IGX-3103 and antiFab nanobody==
<StructureSection load='9ncd' size='340' side='right'caption='[[9ncd]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ncd]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Arachis_hypogaea Arachis hypogaea], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9NCD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9NCD 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]] 1.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=9ncd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ncd OCA], [https://pdbe.org/9ncd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ncd RCSB], [https://www.ebi.ac.uk/pdbsum/9ncd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ncd ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND AND OBJECTIVES: Nonspecific lipid transfer proteins (nsLTPs) are frequently cross-reactive allergens that hamper diagnosis and avoidance. It is challenging to distinguish cross-reactivity from cosensitization with polyclonal serum owing to the presence of a few promiscuous antibodies or many highly specific antibodies. Objective: We hypothesized that a robust analysis of more human monoclonal antibodies (mAbs) would enable us to compare crossreactivity with cosensitization. METHODS: Human monoclonal antibodies were cloned from allergic patients via single cell sequencing and screened for affinity to extracts and recombinant allergens. Ara h 9 was expressed and crystallized with the mAb IGX-3103. Affinity for nsLTPs was explored using molecular modeling, site-directed mutagenesis, and ELISA. RESULTS: A human IgG4 mAb named IGX-3103 was discovered from a type 2-polarized memory B cell expressing CD23, IL-4Ra, and germline IGHE. IGX-3103 bound to 19 different type 1 nsLTP allergens and to extracts from sources without a characterized nsLTP allergen. The structure showed that IGX-3103 induced a conformational change in Ara h 9, enabling a hydrophobic residue from the antibody, Phe104, to enter the lipid binding cavity. Key residues in the epitope were identified to include Leu1, Ser2, Cys3, Lys39, and Asp43 in Ara h 9; these residues are conserved across type 1 nsLTPs, thus explaining the promiscuity of IGX-3103. CONCLUSIONS: IGX-3103 is an example of a human mAb with cross-reactivity to pollen, fruit, and seed type 1 nsLTPs. This observation anecdotally supports the possibility that a few promiscuous mAbs could be driving cross-reactivity.


Authors: Pedersen, L.C., Mueller, G.A.
A Human Monoclonal Antibody Displays Promiscuous Binding to Multiple Type 1 nsLTP Allergens.,Leighton GO, Pedersen LC, Min J, Creeks P, Gabel SA, Perera L, Randall TA, Petrovich RM, Hamilton RG, Croote D, Mueller GA J Investig Allergol Clin Immunol. 2026 Feb 9:0. doi: 10.18176/jiaci.1143. PMID:41661651<ref>PMID:41661651</ref>


Description: Crystal structure of the peanut allergen Ara h 9 with bound Fab IGX-3103 and antiFab nanobody
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Pedersen, L.C]]
<div class="pdbe-citations 9ncd" style="background-color:#fffaf0;"></div>
[[Category: Mueller, G.A]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Arachis hypogaea]]
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Mueller GA]]
[[Category: Pedersen LC]]
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