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

R Furmonaviciene and F Shakib

Division of Molecular and Clinical Immunology, Faculty of Medicine and Health Sciences, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK

Correspondence to:
Dr Shakib farouk.shakib{at}nottingham.ac.uk

Background—Although a large number of allergens have been characterised, the structural, functional, and biochemical features that these molecules have in common, and that could explain their ability to elicit powerful IgE antibody responses, are still uncertain. Recently, there has been considerable 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 production.

Aims—To search for remote homologues of Der p 1 with sequences similar to the 30 conserved amino acids surrounding the catalytic cysteine residue (Cys34).

Methods—Potential homologues were analysed by examining their three dimensional structures and multiple sequence alignments using the programs PROPSEARCH, 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 –ß motif, between an helix on one side and an antiparallel ß sheet on the other side. A similar common motif (a cysteine stabilised –ß fold) can also be found in some toxins and defensins.

Conclusion—Allergens of diverse sources have a common structural motif, namely a groove located inside an –ß motif, which could potentially serve as a ligand binding site.

Key Words: allergen • Der p 1 • protease • three dimensional protein structure

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