The importance of the 2S albumins for allergenicity and cross-reactivity of peanuts, tree nuts, and sesame seeds

Dreskin, Stephen C.; Koppelman, Stef J.; Andorf, Sandra; Nadeau, Kari; Kalra, Anjeli; Braun, Werner; Negi, Surendra S.; Chen, Xueni; Schein, Catherine H.

doi:10.1016/j.jaci.2020.11.004

Cited by 56 publications

(61 citation statements)

References 133 publications

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“…Computational tools have helped to deep in the structural characteristics of proteins and the implications for their allergenicity [31]. Amino acid sequence alignment revealed that only residues surrounding the cysteine patterns exhibit higher identities when comparing with the whole sequence.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Relevant Biomarkers for the Diagnosis of Food Allergies: An Overview of the 2S Albumin Family

Bueno‐Díaz

Martín‐Pedraza

Parrón

et al. 2021

Foods

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2S albumins are relevant and often major allergens from several tree nuts and seeds, affecting mainly children and young people. The present study aims to assess how the structural features of 2S albumins could affect their immunogenic capacity, which is essential to comprehend the role of these proteins in food allergy. For this purpose, twelve 2S albumins were isolated from their respective extracts by chromatographic methods and identified by MALDI-TOF mass-spectrometry. Their molecular and structural characterization was conducted by electrophoretic, spectroscopic and in silico methods, showing that these are small proteins that comprise a wide range of isoelectric points, displaying a general high structure stability to thermal treatment. Despite low amino acid sequence identity, these proteins share structural features, pointing conformational epitopes to explain cross-reactivity between them. Immunoblotting with allergic patients’ sera revealed those possible correlations between evolutionarily distant 2S albumins from different sources. The availability of a well-characterized panel of 2S albumins from plant-derived sources allowed establishing correlations between their structural features and their allergenic potential, including their role in cross-reactivity processes.

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Section: Discussionmentioning

confidence: 99%

Characterization of Relevant Biomarkers for the Diagnosis of Food Allergies: An Overview of the 2S Albumin Family

Bueno‐Díaz

Martín‐Pedraza

Parrón

et al. 2021

Foods

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“…While allergens from PNs and TNs can be grouped into similar protein families, their overall sequence identity falls well below the 70% threshold previously considered to support cross-reactivity, raising questions regarding the basis for this phenomenon [6]. Dreskin et al [7] suggest that the highly conserved cysteine motif structure of 2S albumins, which supports intervening amino acids with similar physicochemical properties (PCPs), is essential for IgE crossreactivity between PN and TNs. The cysteine-rich leader sequences (LS's) from viclin seed storage proteins could potentially harbour similar interactions, further contruibuting to PN/TN cross-reactivity.…”

Section: Discussionmentioning

confidence: 99%

“…Another consequence of the LS architecture is that its defining α-hairpin scaffold is maintained by only a few conserved interactions, allowing it to accumulate mutations over time without compromising its underlying structure. The resulting sequence diversity could allow LSs to mimic the surface features of unrelated proteins, giving rise to cross-reactivity between different allergen families as observed between J2LS and Ara h 2, as the most conserved region of Ara h 2 contains a similar pattern of cysteine residues separated by variable residues [7,37].…”

Section: Discussionmentioning

confidence: 99%

Structure and IgE cross-reactivity among walnut and peanut vicilin leader sequences

Nesbit

Gipson

et al. 2021

Preprint

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Background: Vicilin seed storage proteins are translated with N-terminal leader sequences (LSs) that are cleaved to yield the mature protein. These LSs were thought to be unstructured and rapidly degraded. However, Ara h 1 and Jug r 2 LS (A1LS, J2LS) have been identified in seeds, and immunodominant IgE epitopes detected. Here, common sequences containing structured CxxxC-repeat motifs were identified as potential mediators of IgE cross-reactivity despite very low (17%) sequence identity. Method: Linear IgE epitopes were identified by peptide microarrays, in which overlapping 15-mer peptides on glass slides, were incubated with sera from peanut, walnut or dual allergic individuals. Similar epitopes were computationally predicted. Peanut A1LS and walnut J2LS fragments (J2.1, J2.2, J2.3) each with a CxxxC vicilin LS motif were identified, cloned, expressed, purified and their structures solved using solution-NMR to locate and assess epitopes on the structure. Results: A1LS and J2LSs reveal similar helix-turn-helix motifs connected by disulfide bonds between adjacent CxxxC repeats forming α-hairpin structures. Peanut-allergic IgE bound more frequently to the J2LSs, regardless of walnut allergic status or A1LS binding. IgE binding pattern to peptides from both J2LS and A1LS, along with structure and computational predictions, suggest that the structure and conserved amino acid properties of peptides determine cross-reactivity. The properties of LS IgE epitopes were closely related to epitopes in 2S albumins. Conclusion: The shared α-hairpin structure is a stable scaffold that contributes to cross-reactivity despite low sequence identity. Biophysical properties are a better predictor of distant cross-reactivity than traditional measures of evolutionary conservation.

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“…The majority of nut allergens have been found to be proteins, belonging to the families of 2S albumins, vicilins, legumes and more generally seed storage proteins [ 7 , 10 ]. Previous studies documented solid proof that the 2S albumins are the most relevant nut allergens and highlighted how the structural similarities between the 2S albumins might explain the observed clinical cross-reactivity [ 7 , 11 ]. Table S1 ( Supplementary Materials ) presents the complete list of the allergenic proteins of almond, cashew, hazelnut, peanut, pistachio and walnut.…”

Section: Introductionmentioning

confidence: 99%

Effect of Sample Preparation on the Detection and Quantification of Selected Nuts Allergenic Proteins by LC-MS/MS

et al. 2021

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The detection and quantification of nut allergens remains a major challenge. The liquid chroma-tography tandem mass spectrometry (LC-MS/MS) is emerging as one of the most widely used methods, but sample preparation prior to the analysis is still a key issue. The objective of this work was to establish optimized protocols for extraction, tryptic digestion and LC-MS analysis of almond, cashew, hazelnut, peanut, pistachio and walnut samples. Ammonium bicar-bonate/urea extraction (Ambi/urea), SDS buffer extraction (SDS), polyvinylpolypyrroli-done (PVPP) extraction, trichloroacetic acid/acetone extraction (TCA/acetone) and chloro-form/methanol/sodium chloride precipitation (CM/NaCl) as well as the performances of con-ventional tryptic digestion and microwave-assisted breakdown were investigated. Overall, the protein extraction yields ranged from 14.9 ± 0.5 (almond extract from CM/NaCl) to 76.5 ± 1.3% (hazelnut extract from Ambi/urea). Electrophoretic profiling showed that the SDS extraction method clearly presented a high amount of extracted proteins in the range of 0–15 kDa, 15–35 kDa, 35–70 kDa and 70–250 kDa compared to the other methods. The linearity of the LC-MS methods in the range of 0 to 0.4 µg equivalent defatted nut flour was assessed and recovery of internal standards GWGG and DPLNV(d8)LKPR ranged from 80 to 120%. The identified bi-omarkers peptides were used to relatively quantifier selected allergenic protein form the inves-tigated nut samples. Considering the overall results, it can be concluded that SDS buffer allows a better protein extraction from almond, peanut and walnut samples while PVPP buffer is more appropriate for cashew, pistachio and hazelnut samples. It was also found that conventional overnight digestion is indicated for cashew, pistachio and hazelnut samples, while microwave assisted tryptic digestion is recommended for almond, hazelnut and peanut extracts.

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The importance of the 2S albumins for allergenicity and cross-reactivity of peanuts, tree nuts, and sesame seeds

Cited by 56 publications

References 133 publications

Characterization of Relevant Biomarkers for the Diagnosis of Food Allergies: An Overview of the 2S Albumin Family

Characterization of Relevant Biomarkers for the Diagnosis of Food Allergies: An Overview of the 2S Albumin Family

Structure and IgE cross-reactivity among walnut and peanut vicilin leader sequences

Effect of Sample Preparation on the Detection and Quantification of Selected Nuts Allergenic Proteins by LC-MS/MS

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