Contributions and Future Directions for Structural Biology in the Study of Allergens

Mueller, Geoffrey A.

doi:10.1159/000481078

Cited by 21 publications

(15 citation statements)

References 81 publications

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“…Allergens have emerged as important class of antigens, because they bind to the antibody isotype Immunoglobulin E (IgE). The symptoms associated with allergy are caused by cross-linking of IgE on effector cells ( Mueller, 2017 ). The number of available different allergen structures has increased significantly, and this experimental structural information has provided more insights in understanding allergic disease ( Pomés et al.…”

Section: Introductionmentioning

confidence: 99%

“…Various structural studies focused on understanding antibody specificity and cross-reactivity and observed antigen-antibody interactions at atomistic level ( Dall’Antonia et al. , 2014 ; Mueller, 2017 ; Tscheppe and Breiteneder, 2017 ). Recent antibody-allergen crystal structures provided detailed epitope information, insights in antibody recognition of complex molecular surfaces and an idea of the possible number of epitopes recognizable by the same antibody ( Droupadi et al.…”

Section: Introductionmentioning

confidence: 99%

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Conformational selection of allergen-antibody complexes—surface plasticity of paratopes and epitopes

Fernández‐Quintero

Loeffler

Waibl

et al. 2019

Protein Engineering, Design and Selection

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Antibodies have the ability to bind various types of antigens and to recognize different antibody-binding sites (epitopes) of the same antigen with different binding affinities. Due to the conserved structural framework of antibodies, their specificity to antigens is mainly determined by their antigen-binding site (paratope). Therefore, characterization of epitopes in combination with describing the involved conformational changes of the paratope upon binding is crucial in understanding and predicting antibody-antigen binding. Using molecular dynamics simulations complemented with strong experimental structural information, we investigated the underlying binding mechanism and the resulting local and global surface plasticity in the binding interfaces of distinct antibody-antigen complexes. In all studied allergen-antibody complexes, we clearly observe that experimentally suggested epitopes reveal less plasticity, while non-epitope regions show high surface plasticity. Surprisingly, the paratope shows higher conformational diversity reflected in substantially higher surface plasticity, compared to the epitope. This work allows a visualization and characterization of antibody-antigen interfaces and might have strong implications for antibody-antigen docking and in the area of epitope prediction.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Conformational selection of allergen-antibody complexes—surface plasticity of paratopes and epitopes

Fernández‐Quintero

Loeffler

Waibl

et al. 2019

Protein Engineering, Design and Selection

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“…While the presence of isoallergens and their variants is challenging for standardization of extracts [264] and allergy diagnostics, it is also fascinating from the perspective of molecular allergology and the origin of an allergic disease, because despite their similarities, these molecules can display different behaviors when in contact with the human immune system [102, 265, 266]. This difference in behavior may be key to understanding the allergy origin and key in the design of immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

A robust method for the estimation and visualization of IgE cross-reactivity likelihood between allergens belonging to the same protein family

et al. 2018

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Among the vast number of identified protein families, allergens emanate from relatively few families which translates to only a small fraction of identified protein families. In allergy diagnostics and immunotherapy, interactions between immunoglobulin E and allergens are crucial because the formation of an allergen-antibody complex is necessary for triggering an allergic reaction. In allergic diseases, there is a phenomenon known as cross-reactivity. Cross-reactivity describes a situation where an individual has produced antibodies against a particular allergenic protein, but said antibodies fail to discriminate between the original sensitizer and other similar proteins that usually belong to the same family. To expound the concept of cross-reactivity, this study examines ten protein families that include allergens selected specifically for the analysis of cross-reactivity. The selected allergen families had at least 13 representative proteins, overall folds that differ significantly between families, and include relevant allergens with various potencies. The selected allergens were analyzed using information on sequence similarities and identities between members of the families as well as reports on clinically relevant cross-reactivities. Based on our analysis, we propose to introduce a new A-RISC index (Allergens’–Relative Identity, Similarity and Cross-reactivity) which describes homology between two allergens belonging to the same protein family and is used to predict the likelihood of cross-reactivity between them. Information on sequence similarities and identities, as well as on the values of the proposed A-RISC index is used to introduce four categories describing a risk of a cross-reactive reaction, namely: high, medium-high, medium-low and low. The proposed approach can facilitate analysis in component-resolved allergy diagnostics, generation of avoidance guidelines for allergic individuals, and help with the design of immunotherapy.

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“…Another emerging structural technique that could contribute to IgE epitope mapping is cryo-electron microscopy (cryo-EM). In this technique, the proteins do not need to be crystallized, but instead are instantly flash-frozen into vitrified ice, allowing to work with much larger biomolecular complexes and much less sample than the required for crystallography (Mueller 2017). Therefore, it opens an opportunity to directly examine the structure of an IgE molecule in complex with an allergen.…”

Section: Cryo-electron Microscopy Coupled To Mass Spectrometrymentioning

confidence: 99%

New applications of advanced instrumental techniques for the characterization of food allergenic proteins

Benedé

Lozano‐Ojalvo

Cristóbal

et al. 2021

Critical Reviews in Food Science and Nutrition

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Current approaches based on electrophoretic, chromatographic or immunochemical principles have allowed characterizing multiple allergens, mapping their epitopes, studying their mechanisms of action, developing detection and diagnostic methods and therapeutic strategies for the food and pharmaceutical industry. However, some of the common structural features related to the allergenic potential of food proteins remain unknown, or the pathological mechanism of food allergy is not yet fully understood. In addition, it is also necessary to evaluate new allergens from novel protein sources that may pose a new risk for consumers. Technological development has allowed the expansion of advanced technologies for which their whole potential has not been entirely exploited and could provide novel contributions to still unexplored molecular traits underlying both the structure of food allergens and the mechanisms through which they sensitize or elicit adverse responses in human subjects, as well as improving analytical techniques for their detection. This review presents cutting-edge instrumental techniques recently applied when studying structural and functional aspects of proteins, mechanism of action and interaction between biomolecules. We also exemplify their role in the food allergy research and discuss their new possible applications in several areas of the food allergy field.

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Contributions and Future Directions for Structural Biology in the Study of Allergens

Cited by 21 publications

References 81 publications

Conformational selection of allergen-antibody complexes—surface plasticity of paratopes and epitopes

Conformational selection of allergen-antibody complexes—surface plasticity of paratopes and epitopes

A robust method for the estimation and visualization of IgE cross-reactivity likelihood between allergens belonging to the same protein family

New applications of advanced instrumental techniques for the characterization of food allergenic proteins

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