100 Years later: Celebrating the contributions of x-ray crystallography to allergy and clinical immunology

Abstract

Current knowledge of molecules involved in immunology and allergic disease results from significant contributions of X-ray crystallography, a discipline that just celebrated its 100th anniversary. The histories of allergens and X-ray crystallography are intimately intertwined. The first enzyme structure to be determined was lysozyme, also known as the chicken food allergen Gal d 4. Crystallography determines the exact three-dimensional positions of atoms in molecules. Structures of molecular complexes in the disciplines of immunology and allergy have revealed the atoms involved in molecular interactions and in mechanisms of disease. These complexes include peptides presented by MHC class II molecules, cytokines bound to their receptors, allergen-antibody complexes, and innate immune receptors with their ligands. The information derived from crystallographic studies provides insights into the function of molecules. Allergen function is one of the determinants of environmental exposure, which is essential for IgE sensitization. Proteolytic activity of allergens or their capacity to bind lipopolysaccharides may also contribute to allergenicity. The atomic positions define the molecular surface that is accessible to antibodies. This surface in turn determines antibody specificity and cross-reactivity that are important factors for the selection of allergen panels used for molecular diagnosis and for the interpretation of clinical symptoms. This review celebrates the contributions of X-ray crystallography to clinical immunology and allergy, focusing on new molecular perspectives that influence the diagnosis and treatment of allergic diseases.

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“…In this report, an overview of the most important indoor allergens is presented, together with an update on the most current cutting edge research on their molecular structure and function (Table 1) [3•] and approaches to assess and treat indoor allergies.…”

On the evolution of the quality of macromolecular models in the PDB

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“…Structural biology has fulfilled a history-changing mission in science at the interface of physics, chemistry, and biology when for over six decades it has maintained its leading role in providing the structural basis for our understanding of life [1][2][3][4]. Its results were always regarded as exceptionally solid, and created a gold standard in biological research, almost unattainable in many other areas of life sciences.…”

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

“…For evidence of this, there are approximately 100 allergen structures in the protein data bank, but there are less than 10 structures of different allergens in complex with antibodies [71]. The review of Dall’Antonia et al nicely presents high resolution techniques utilizing crystallography and NMR for mapping antigen-antibody epitopes, with particular attention to allergen complexes [72].…”