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Analyzing an allergen

SBKB [doi:10.1038/sbkb.2011.57]
Featured Article - January 2012
Short description: Computational, structural, and biochemical analysis of peanut Ara h 1 gives insights into understanding and diagnosing nut allergies.

A molecular surface representation of the trimeric Ara h 1 core. Figure courtesy of Wladek Minor.

As the incidence of peanut and tree nut allergies rises, pressure is mounting on researchers to understand the mechanisms behind these allergies and provide improved diagnostics and treatments. The two major peanut allergens are the vicilin Ara h 1 and the legumin Ara h 3. Ara h 1 is recognized by IgE present in sera from 90% of peanut-allergic individuals. It forms a homotrimer and may form larger oligomers in vivo. How the natural form of peanut Ara h 1 compares to other nut allergens and to recombinant Ara h 1 that can be used in newly developed diagnostic methods remains to be seen.

Minor, Chruszcz and colleagues (PSI NYSGRC) have performed a multifaceted analysis of natural and recombinant peanut Ara h 1. Crystallographic data reveal that the recombinant Ara h 1 core is trimeric and sufficient for formation of larger oligomers. Small angle X-ray scattering data indicate that natural Ara h 1 as well as the recombinant core form larger oligomers containing 9 or 12 protein chains. Interestingly, the full-length recombinant form of Ara h 1 is monomeric and partially unfolded in solution, consistent with in vitro gastric digestion assays that revealed natural Ara h 1 is most stable while full-length recombinant Ara h 1 is least stable. When tested for reactivity to serum IgE from patients with a peanut allergy, full-length recombinant Ara h 1 was reactive for most individuals, although natural Ara h 1 was reactive for all patients and usually produced a stronger reaction than recombinant Ara h 1. The shortened recombinant core of Ara h 1 also reacted with patient sera, with a pattern similar to that of full-length recombinant Ara h 1.

The authors find strong sequence and structural similarities between Ara h 1 and other vicilins and legumins, consistent with previously reported shared IgE-binding epitopes between peanuts and tree nut allergens; this helps explain how patients with peanut allergies often have allergies to other nuts as well. However, the finding that recombinant Ara h 1 was not recognized by patient sera as strongly as natural Ara h 1 has important clinical implications, and the differences between recombinant and natural Ara h 1 reported here need to be taken into account in the refinement of new diagnostic methods.

Steve Mason

References

  1. M. Chruszcz et al. Structural and Immunologic Characterization of Ara h 1, a Major Peanut Allergen.
    J. Biol. Chem. 286, 39318-39327 (2011). doi:10.1074/jbc.M111.270132

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