Allergens from cockroaches cause major asthma-related health problems worldwide. Among them Per a
3 belongs to the most potent allergens. Although the sequences of some members of the Per a 3-family
are known, their biochemical and biophysical properties have not been investigated. Here we present for
the first time a thorough structural characterization of these allergens, which have recently been tested
to induce an increase of allergy specific indicators in blood of Europeans. We isolated two Per a 3
isoforms, which occur freely dissolved in the hemolymph as hexamers with molecular masses of
465 25 kDa (P II) and 512 25 kDa (P I). Their sedimentation coefficients (S20,W) were determined to be
17.4 0.7 S (P II) and 19.0 0.9 S (P I), respectively. Sequence analysis revealed that P II consists of two
subunit types known as allergens Per a 3.01 and Per a 3.0201, while PI consists of a new allergenic subunit
type designated as Per a 3.03. A 3D model of the hexameric allergen Per a 3 was obtained by homology
modelling. Almost all of the recently predicted 11 putative antigenic peptides and reported IgE-epitopes
could be located on the surface of the hexamer, thus being freely accessible in the hexameric structure of the
native molecules. We propose this might contribute to their allergic potential as well as their extreme
stability with respect to temperature.