The molecular basis of allergenicity: comparative analysis of the three dimensional structures of diverse allergens reveals a common structural motif

Background-Although a large number of allergens have been characterised, th e structural, functional, and biochemical features that these molecules hav e in common, and that could explain their ability to elicit powerful IgE an tibody responses, are still uncertain. Recently, there has been considerabl e interest in the role of the cysteine protease activity of the house dust mite allergen Der p 1 in biasing the immune response in favour of IgE produ ction. Aims-To search for remote homologues of Der p 1 with sequences similar to t he 30 conserved amino acids surrounding the catalytic cysteine residue (Cys 34). Methods-Potential homologues were analysed by examining their three dimensi onal structures and multiple sequence alignments using the programs PROP-SE ARCH, ClustalW, GeneDoc, and Swiss Pdb Viewer. Results-Diverse allergens (for example, the plant cysteine protease papain, the transport protein lipocalin Mus m 1, and the ragweed allergen Amb a 5) have a similar structural motif; namely, a groove resembling the substrate binding groove of Der p 1. The groove is located inside an alpha-beta moti f, between an alpha helix on one side and an antiparallel beta sheet on the other side. A similar common motif (a cysteine stabilised alpha-beta fold) can also be found in some toxins and defensins. Conclusion-Allergens of diverse sources have a common structural motif, nam ely a groove located inside an alpha-beta motif, which could potentially se rve as a ligand binding site.