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Dimerization of lipocalin allergens.

Niemi MH, Rytkönen-Nissinen M, Miettinen I, Jänis J, Virtanen T, Rouvinen J - Sci Rep (2015)

Bottom Line: We have determined two different dimeric crystal structures for bovine dander lipocalin Bos d 2, which was earlier described as a monomeric allergen.The crystal structure analysis of all other determined lipocalin allergens also revealed oligomeric structures which broadly utilize inherent structural features of the β-sheet in dimer formation.According to the moderate size of monomer-monomer interfaces, most of these dimers would be transient in solution.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biocenter Kuopio, University of Eastern Finland, PO BOX 111, 80101 Joensuu, Finland.

ABSTRACT
Lipocalins are one of the most important groups of inhalant animal allergens. The analysis of structural features of these proteins is important to get insights into their allergenicity. We have determined two different dimeric crystal structures for bovine dander lipocalin Bos d 2, which was earlier described as a monomeric allergen. The crystal structure analysis of all other determined lipocalin allergens also revealed oligomeric structures which broadly utilize inherent structural features of the β-sheet in dimer formation. According to the moderate size of monomer-monomer interfaces, most of these dimers would be transient in solution. Native mass spectrometry was employed to characterize quantitatively transient dimerization of two lipocalin allergens, Bos d 2 and Bos d 5, in solution.

No MeSH data available.


Related in: MedlinePlus

The sketch for the initial events leading to the allergen triggered signal transduction.(a) allergen-specific IgE serum antibodies bind to FcεRI receptors on the surface of mast cells or basophils with high affinity. (b) allergen exposure leads to a binding of monomeric allergens to specific IgE antibodies already bound to FcεRI receptors. (c) tethering of monomeric allergens on the cell surface results in dimerization of allergen monomers. The 2-dimensional dissociation constant for allergen dimers on the cell surface is not known. (d) the allergen dimerization has cross-linked FcεRI bound IgE antibodies that lead to the signal transduction.
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f6: The sketch for the initial events leading to the allergen triggered signal transduction.(a) allergen-specific IgE serum antibodies bind to FcεRI receptors on the surface of mast cells or basophils with high affinity. (b) allergen exposure leads to a binding of monomeric allergens to specific IgE antibodies already bound to FcεRI receptors. (c) tethering of monomeric allergens on the cell surface results in dimerization of allergen monomers. The 2-dimensional dissociation constant for allergen dimers on the cell surface is not known. (d) the allergen dimerization has cross-linked FcεRI bound IgE antibodies that lead to the signal transduction.

Mentions: If we sketch the initial process leading to the mast-cell degranulation we can first note that serum IgE antibodies bind very strongly to the FcεRI receptors on the surface of mast cells or basophils (KD ∼ 0.1 nM) (Fig. 6a). In addition, the binding of allergens to IgE antibodies is also potent (KD ∼ 0.1–1.0 nM) (Fig. 6b), generally more potent than antigen binding to IgG antibodies115. Both these interactions are many order of magnitudes stronger than transient dimerization of allergens (KD ∼ 10 μM) in solution. Therefore, we can assume that IgE antibodies are predominantly bound to the FcεRI receptors on the cell surface and the allergen prefers to bind as a monomer to the surface bound specific high-affinity IgE-antibodies (Fig. 6b). We could consider that this process leads to colocalization30 of allergens, thus they increase their “concentration” on the surface of mast cells, allowing the dimerization to occur (Fig. 6c,d).


Dimerization of lipocalin allergens.

Niemi MH, Rytkönen-Nissinen M, Miettinen I, Jänis J, Virtanen T, Rouvinen J - Sci Rep (2015)

The sketch for the initial events leading to the allergen triggered signal transduction.(a) allergen-specific IgE serum antibodies bind to FcεRI receptors on the surface of mast cells or basophils with high affinity. (b) allergen exposure leads to a binding of monomeric allergens to specific IgE antibodies already bound to FcεRI receptors. (c) tethering of monomeric allergens on the cell surface results in dimerization of allergen monomers. The 2-dimensional dissociation constant for allergen dimers on the cell surface is not known. (d) the allergen dimerization has cross-linked FcεRI bound IgE antibodies that lead to the signal transduction.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561914&req=5

f6: The sketch for the initial events leading to the allergen triggered signal transduction.(a) allergen-specific IgE serum antibodies bind to FcεRI receptors on the surface of mast cells or basophils with high affinity. (b) allergen exposure leads to a binding of monomeric allergens to specific IgE antibodies already bound to FcεRI receptors. (c) tethering of monomeric allergens on the cell surface results in dimerization of allergen monomers. The 2-dimensional dissociation constant for allergen dimers on the cell surface is not known. (d) the allergen dimerization has cross-linked FcεRI bound IgE antibodies that lead to the signal transduction.
Mentions: If we sketch the initial process leading to the mast-cell degranulation we can first note that serum IgE antibodies bind very strongly to the FcεRI receptors on the surface of mast cells or basophils (KD ∼ 0.1 nM) (Fig. 6a). In addition, the binding of allergens to IgE antibodies is also potent (KD ∼ 0.1–1.0 nM) (Fig. 6b), generally more potent than antigen binding to IgG antibodies115. Both these interactions are many order of magnitudes stronger than transient dimerization of allergens (KD ∼ 10 μM) in solution. Therefore, we can assume that IgE antibodies are predominantly bound to the FcεRI receptors on the cell surface and the allergen prefers to bind as a monomer to the surface bound specific high-affinity IgE-antibodies (Fig. 6b). We could consider that this process leads to colocalization30 of allergens, thus they increase their “concentration” on the surface of mast cells, allowing the dimerization to occur (Fig. 6c,d).

Bottom Line: We have determined two different dimeric crystal structures for bovine dander lipocalin Bos d 2, which was earlier described as a monomeric allergen.The crystal structure analysis of all other determined lipocalin allergens also revealed oligomeric structures which broadly utilize inherent structural features of the β-sheet in dimer formation.According to the moderate size of monomer-monomer interfaces, most of these dimers would be transient in solution.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biocenter Kuopio, University of Eastern Finland, PO BOX 111, 80101 Joensuu, Finland.

ABSTRACT
Lipocalins are one of the most important groups of inhalant animal allergens. The analysis of structural features of these proteins is important to get insights into their allergenicity. We have determined two different dimeric crystal structures for bovine dander lipocalin Bos d 2, which was earlier described as a monomeric allergen. The crystal structure analysis of all other determined lipocalin allergens also revealed oligomeric structures which broadly utilize inherent structural features of the β-sheet in dimer formation. According to the moderate size of monomer-monomer interfaces, most of these dimers would be transient in solution. Native mass spectrometry was employed to characterize quantitatively transient dimerization of two lipocalin allergens, Bos d 2 and Bos d 5, in solution.

No MeSH data available.


Related in: MedlinePlus