Crystal Structure of Der f 7, a Dust Mite Allergen from Dermatophagoides farinae

Abstract

BackgroundDer f 7 is the group 7 allergen from the dust mite Dermatophagoides farinae, homologous to the major allergen Der p 7 from D. pteronyssinus. Monoclonal antibody that bind to residues Leu48 and Phe50 was found to inhibit IgE binding to residue Asp159, which is important for the cross-reactivity between Der f 7 and Der p 7.Methodology/Principal FindingsHere, we report the crystal structure of Der f 7 that shows an elongated and curved molecule consisting of two anti-parallel β-sheets – one 4-stranded and the other 5-stranded – that wrap around a long C-terminal helix. The overall fold of Der f 7 is similar to Der p 7 but key difference was found in the β1–β2 loop region. In Der f 7, Leu48 and Phe50 are in close proximity to Asp159, explaining why monoclonal antibody binding to Leu48 and Phe50 can inhibit IgE binding to Asp159. Both Der f 7 and Der p 7 bind weakly to polymyxin B via a similar binding site that is formed by the N-terminal helix, the 4-stranded β-sheet and the C-terminal helix. The thermal stability of Der f 7 is significantly lower than that of Der p 7, and the stabilities of both allergens are highly depend on pH.Conclusion/SignificanceDer f 7 is homologous to Der p 7 in terms of the amino acid sequence and overall 3D structure but with significant differences in the region proximal to the IgE epitope and in thermal stability. The crystal structure of Der f 7 provides a basis for studying the function and allergenicity of this group of allergens.

Do lipids influence the allergic sensitization process?

“…The fold of Der p 7 resembles that of the LPS-binding protein, which interacts with TLR4 after binding LPS and other bacterially derived lipid ligands 11 . However, Der p 7 did not bind LPS but bound the bacterial lipopeptide polymyxin B with weak affinity, as was shown for Der f 7 as well 59 . Interestingly, a D pteronyssinus extract induced signaling through TLR2 and TLR4 in the mouse alveolar macrophage cell line MH-S 60 .…”

Ancestral reconstruction of tick lineages

“…Graphical representations of unfed (bottom left) and acini after apocrine secretion (bottom right). ND -not determined (Tan et al 2012). …”

Hierarchy and molecular properties of house dust mite allergens

“…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.…”

“…5 The lesser concordance might result from the high degree of cockroach and B. tropicalis sensitisation in Sao Paulo, for example cross-reactivity with Blo t 21. 48 Similarly Singapore where only 78% of subjects had IgE binding to a combination of Der p 1&2 8 has a high prevalent sensitisation to B. tropicalis.…”