The structure of the dust mite allergen Der p 7 reveals similarities to innate immune proteins

Mueller, Geoffrey A.; Edwards, Lori L.; Aloor, Jim J.; Fessler, Michael B.; Glesner, Jill; Pomés, Anna; Chapman, Martin D.; London, Robert E.; Pedersen, Lars C.

doi:10.1016/j.jaci.2009.12.016

Cited by 98 publications

(98 citation statements)

References 64 publications

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“…For example, Der p 2 functionally substituted for murine MD-2, an innate immune protein known to bind a lipopolysaccharide-binding protein from Gram-negative bacteria (18). Similarly, the structure of Der p 7 resembles lipopolysaccharide-binding protein, and Der p 7 was shown to bind a lipopeptide from Gram-positive bacteria (17). The structure of Der p 5 presented here suggests that a Der p 5 dimer may also have a propensity to bind hydrophobic compounds.…”

Section: Discussionmentioning

confidence: 80%

“…Recently, crystallographic studies revealed that Der p 7 was distantly related to hydrophobic ligand-binding proteins of the human innate immune system (17); this relationship was not previously identified from sequence information alone. It was suggested that Der p 7 may co-opt the innate immune response into promoting allergenicity through the binding and delivery of hydrophobic ligands (17), as has been demonstrated for the mite allergen Der p 2 (18).…”

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confidence: 97%

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

Mueller

Gosavi

Krahn

et al. 2010

Journal of Biological Chemistry

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Group 5 allergens from house dust mites elicit strong IgE antibody binding in mite-allergic patients. The structure of Der p 5 was determined by x-ray crystallography to better understand the IgE epitopes, to investigate the biologic function in mites, and to compare with the conflicting published Blo t 5 structures, designated 2JMH and 2JRK in the Protein Data Bank. Der p 5 is a three-helical bundle similar to Blo t 5, but the interactions of the helices are more similar to 2JMH than 2JRK. The crystallographic asymmetric unit contains three dimers of Der p 5 that are not exactly alike. Solution scattering techniques were used to assess the multimeric state of Der p 5 in vitro and showed that the predominant state was monomeric, similar to Blo t 5, but larger multimeric species are also present. In the crystal, the formation of the Der p 5 dimer creates a large hydrophobic cavity of ϳ3000 Å 3 that could be a ligand-binding site. Many allergens are known to bind hydrophobic ligands, which are thought to stimulate the innate immune system and have adjuvant-like effects on IgE-mediated inflammatory responses.

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Section: Discussionmentioning

confidence: 80%

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confidence: 97%

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

Mueller

Gosavi

Krahn

et al. 2010

Journal of Biological Chemistry

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“…They all contain conserved LBP/BPI domains. In this regard, Fel d 8 is similar to the group 7 allergens of HDMs [27]. Neither latherin nor Der p 7 have been shown to bind enterobacterial LPS, but Der p 7 has been shown to bind the lipopeptide polymyxin B.…”

Section: Discussionmentioning

confidence: 99%

Two Newly Identified Cat Allergens: The von Ebner Gland Protein Fel d 7 and the Latherin-Like Protein Fel d 8

Smith

O’Neil

Hales

et al. 2011

Int Arch Allergy Immunol

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Introduction: Characterization of the complete IgE binding spectrum of cat allergens is important for the development of improved diagnosis and effective immunotherapeutics. While Fel d 1 remains unchallenged as the major cat allergen, we now report the isolation of two new allergens capable of binding similar concentrations of IgE in the allergic sera of some individuals. Materials and Methods: Cat tongue and submandibular salivary gland cDNA libraries were screened by DNA hybridisation and IgE immunoassay. The isolated DNA fragments were sub-cloned into an E. coli expression system and the IgE reactivity was examined with human cat-allergic sera using a DELFIA IgE quantitation assay. Results: Fel d 7, an 18 kDa von Ebner gland protein Can f 1 homologue, was isolated from the tongue library. Fel d 8, a 24-kDa latherin-like protein with homology to Equ c 5, was isolated from the submandibular library. The frequency of IgE binding of cat-allergic sera to recombinant Fel d 1, 7 and 8 was 60.5, 37.6 and 19.3%, respectively. Inhibition studies indicated some IgE binding cross-reactivity between Fel d 7 and dog dander extracts. Discussion: The study reports the isolation and characterization of two new cat allergens. The isolation of these allergens provides the opportunity to determine the role that IgE binding proteins other than Fel d 1 play in cat-allergic disease. For cat-allergic individuals with moderate to mild rhinoconjunctivitis these allergens may play a more important role in the manifestation of their allergic disease.

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“…The group 7 structures show these uniquely Arachnida proteins to be members of the LPS-binding/bactericidal permeability inducing proteins 47,48 with similarities to insect odorant binding proteins that include hormone receptors. 49 They have elongated structures with antiparallel beta-sheets wrapped around a helix to create a lipid-binding domain.…”

Section: Group 7 Allergensmentioning

confidence: 99%

Hierarchy and molecular properties of house dust mite allergens

Thomas

2015

Allergology International

152

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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The structure of the dust mite allergen Der p 7 reveals similarities to innate immune proteins

Cited by 98 publications

References 64 publications

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

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

Two Newly Identified Cat Allergens: The von Ebner Gland Protein Fel d 7 and the Latherin-Like Protein Fel d 8

Hierarchy and molecular properties of house dust mite allergens

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