The vicilins from peanut and walnut are considered major allergens and are translated with N-terminal leader sequences (LS) that are cleaved to yield the mature protein. These LS were thought to be degraded and unstructured, but western blots and mass spectrometry demonstrate the presence of discrete ~7 kDa LS fragments in peanut and walnut seeds. Additionally, previous work suggested they might contain immunoreactive epitopes, and possibly be a source of cross-reactivity despite very low (&lt;20%) overall sequence identity; this suggested the presence of structured elements. To explore a possible structural basis for cross-reactivity, the structures of the peanut LS (A1LS) and three walnut LS (J2LS-1, 2, &3) fragments was solved using solution NMR. Despite the low sequence identity, all four LS’s reveal strikingly similar helix-turn-helix motifs held together by disulfide bonds between adjacent CxxxC repeats. Microarray analysis revealed linear IgE epitopes in the structured regions of A1LS, along with J2LS-1, 2, & 3 that showed reactivity to dual-sensitized, and peanut and walnut exclusive allergic patient sera. Mapping the J2LS epitopes onto the structures revealed strikingly similar physical properties to the A1LS structure, providing a structural basis for the observed cross reactivity in spite of the low sequence identity. In conclusion, the results indicate that CxxxC motifs within the Ara h 1 and Jug r 2 LS give rise to structured regions which support multiple immunodominant IgE epitopes, and appear to be important for the cross-reactivity of nut allergies despite their low sequence identity.<br/>

Molecular characterization of the cross-reactivity between the N-terminal leader sequences of Ara h 1 and Jug r 2

ACS Fall 2020 Virtual Meeting

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