Allergens reveal common contours
Protein shape predicts the difference between peas and peanuts.
Many of the plant proteins that cause allergies have remarkably similar shapes, according to a computer analysis. The study could help scientists to identify new allergens, and explain exactly how they trigger an immune response.
Allergenic proteins are present in many parts of plants, such as grass pollen or apple skin. Although normally harmless, they cause sufferers to generate an immune response as if they had an infection. Symptoms usually include itchy eyes and runny noses, but can be more severe, such as diarrhoea, or even life threatening.
We don't know why otherwise benign proteins cause some people to react in this way. Previous research has focused on the sequence of amino acids that make up the allergens. But scientists often found that very different sequences from unrelated plants triggered almost identical allergic responses.
Biologists had always assumed that the proteins' shapes must play some role, but the new study is the first to quantify the effect, says Clare Mills, an allergy expert at the Institute of Food Research, Norwich, UK, and part of the team that carried out the research. The results are published today in the Journal of Allergy and Clinical Immunology1.
To find out what difference protein shape makes, the researchers used computer models to look at the structures of 129 common food allergens, then classified them according to their surface features. The allergens belonged to only 20 of 3,849 possible protein 'families', and just four families accounted for two-thirds of them.
Mills says she was surprised by how many of the allergens share the same structural features. "Now we need to find out why, and that's not trivial," she adds. She thinks the most active protein shapes may have developed soon after flowering plants evolved, more than 100 million years ago, and been conserved throughout subsequent diversification.
And, says Mills, "if a new protein belongs to one of these families, it has a higher likelihood of being an allergen." So scientists developing genetically modified plants, for example, could use the information to avoid producing proteins that might trigger allergies.
The researchers now plan to catalogue the structures of further allergenic proteins, to help them understand exactly how the different shapes trigger certain immune responses. One question they want to answer is why peanut allergies can be so severe, when the related pea species pose little threat.
- Jenkins, J. A., Griffiths-Jones, S., Shewry, P. R., Breiteneder, H. & Mills, E. N. C. J. Allergy Clin. Immunol. published online doi:10.1016/j/jaci.2004.10.026 (2005).