Der p 5 Crystal Structure Provides Insight into the Group 5 Dust Mite Allergens

Mueller, Geoffrey A.; Gosavi, R.A.; Krahn, J.M.; Edwards, Lori L.; Cuneo, M.J.; Glesner, Jill; Pomés, Anna; Chapman, Martin D.; London, Robert E.; Pedersen, Lars C.

doi:10.1074/jbc.m110.128306

Cited by 50 publications

(69 citation statements)

References 45 publications

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“…There is only a low degree of cross reactivity between Der p 5 and 21 41 and between Der p 5 and Blo t 5 42 but Blo t 21 and Der p 21 cross react. 43 The structure of Der p 5 shows a monomeric bundle of coiled coils that can polymerise to create a 6-member cage with a hydrophobic cavity 44 It agrees with that solved by NMR for Blo t 5 45 and with minor differences with that of Chan et al 46 and they closely resemble the structure of Blo t 21. 43 The group 5&21 allergens are the serodominant allergens of B. tropicalis.…”

Section: Groups 5and21 Allergenssupporting

confidence: 75%

Hierarchy and molecular properties of house dust mite allergens

Thomas

2015

Allergology International

145

141

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The allergenic load of house dust mite allergy is largely constituted by a few proteins with a hierarchical pattern of allergenicity. The serodominant specificities are the group 1&2 and the group 23 faecal allergens. The collective IgE binding to the group 1&2 allergens can measure unequivocal HDM sensitisation better than HDM extracts although discrepancies have been found in regions with complex acarofauna suggesting a need to investigate the specificity with allergen components. The group 4, 5, 7&21 allergens that each induce responses in about 40% of subjects are mid-tier allergens accounting for most of the remaining IgE binding. Their titres are proportional to the concomitant responses to Der p1&2. Group 2 allergen variants have different antibody binding. Body proteins only occasionally induce sensitisation although a higher prevalence of binding by atopic dermatitis patients provides a new avenue of research. A broad spectrum of IgE binding has been associated with diverse symptoms but not with the severity of asthma which is associated with low IgG antibody. Some allergens such as the group 14 large lipid binding proteins and the recently described proteins Der f 24-33, need further investigation but with the cognoscence that other denominated allergens have been found to be minor sensitisers by comparative quantitative analyses. Scabies is a confounder for diagnosis with extracts, inducing cross-reactive antibodies with Der p 4&20 as is seafood allergy with cross reactivity to Der p 10 a minor HDM allergen. The HDM genome sequence can now be used to verify allelic and paralogous variations.

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Section: Groups 5and21 Allergenssupporting

confidence: 75%

Hierarchy and molecular properties of house dust mite allergens

Thomas

2015

Allergology International

145

141

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“…These residues are highlighted in the Blo t 5 3-D structure depicted in Figure 1e, which also shows the flexible N-terminal region and the 3 α-helices, organized in an antiparallel manner to form a coiled-coil helical structure. While the Blo t 5 structure was determined to be monomeric, the structure of Der p 5 is dimeric, which means it has a large hydrophobic cavity that may be a ligand-binding site [48]. These cavities in allergens are normally known to bind hydrophobic ligands, which can influence the innate immune system as well as IgE-mediated diseases [48,49].…”

Section: Allergens Of B Tropicalismentioning

confidence: 99%

“…While the Blo t 5 structure was determined to be monomeric, the structure of Der p 5 is dimeric, which means it has a large hydrophobic cavity that may be a ligand-binding site [48]. These cavities in allergens are normally known to bind hydrophobic ligands, which can influence the innate immune system as well as IgE-mediated diseases [48,49]. To predict if other group 5 mite allergens could form dimers like Der p 5, Khemili et al [50] performed an in silico analysis using MODELLER and the ClusPro server [50,51,52].…”

Section: Allergens Of B Tropicalismentioning

confidence: 99%

Allergens of <b><i>Blomia tropicalis</i></b>: An Overview of Recombinant Molecules

Silva¹,

Asam

Lackner

et al. 2017

Int Arch Allergy Immunol

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Allergic diseases are considered a major problem for healthcare systems in both developed and developing countries. House dust mites are well-known triggers of allergic manifestations. While the Dermatophagoides genus is widely distributed globally, Blomia tropicalis is the most prominent mite species in the tropical and subtropical regions of the world. Over the last decades, an increase in sensitization rates to B. tropicalis has been reported, leading to increased research efforts on Blomia allergens. In fact, 8 new allergens have been identified and characterized to different degrees. Here, we provide an overview of recent developments concerning the identification and production of recombinant Blomia allergens, as well as their structural and immunological characterization. Although considerable progress has been achieved, detailed molecule-based studies are still needed to better define the clinical relevance of Blomia allergens. Thus, the establishment of a well-standardized and fully characterized panel of allergens remains a challenge for the development of better diagnosis and therapy of allergic diseases induced by B. tropicalis.

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“…12,58 While the three-dimensional structures of these and other allergens have been determined, their functions still are not well understood. 10,57,59 Cat allergen Fel d 1 has an uteroglobulin-like fold and consists of a dimer of heterodimers made exclusively of α-helices. Structures of recombinant Fel d 1 made by fusion of the monomers involved in each heterodimer have been determined.…”

Section: Allergen Structure As a Determinant Of Allergic Diseasementioning

confidence: 99%

“…A large hydrophobic cavity formed by each dimer has the potential to bind lipidic ligands. 10 Der p 7 has a similar structure to a LPS-binding protein involved in TLR4 activation, and to the surfactant allergen Equ c 4. 9,77 The fold consists of two 4-stranded antiparallel β-sheets that wrap around a long C-terminal helix (Fig.…”

Section: Influence Of Allergen Function On Allergenicitymentioning

confidence: 99%

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

Pomés

Chruszcz

Gustchina

et al. 2015

Journal of Allergy and Clinical Immunology

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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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Der p 5 Crystal Structure Provides Insight into the Group 5 Dust Mite Allergens

Cited by 50 publications

References 45 publications

Hierarchy and molecular properties of house dust mite allergens

Hierarchy and molecular properties of house dust mite allergens

Allergens of <b><i>Blomia tropicalis</i></b>: An Overview of Recombinant Molecules

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

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