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Team:Linkoping Sweden/Project/Culprit
From 2014.igem.org
The Culprit
A peanut allergy appears early in life and tends to persist indefinitely when compared to other food allergies. Symptoms range from urticaria (hives) to severe, systemic anaphylaxis.
Different proteins are associated with these clinical reactions. The ara h1 protein is an important allergen and is recognized by 90 % of peanut-sensitive persons1. It is 418 amino acids in length and belongs to the vicilin family of seed storage proteins. The structure consists of two sets of opposing antiparallel β-sheets with terminal regions of α-helical bundles (Fig 1). What makes Ara h1 so dangerous to allergic individuals is that it is stable during digestion and survives intact in many food processing methods. It also contains protease digestion sites which are inaccessible due to the compact tertiary structure2.
In an allergic individual, the body thinks that the protein is an immunological threat and generates IgE, immunoglobulin E. IgE binds to ara h1 protein and activates mast cells which releases histamines, causing an allergic reaction. The mast cell receptors cross-link, inducing a signal transduction that results in degranulation (Fig 2). Ara h1 protein consists of 23 IgE-binding epitopes, varying from 6-8 aminoacids in length. There is no common amino acid sequence between the epitopes. The most critical part of the sequence is the hydrophobic residues. It has been shown that substitution of a single amino acid leads to loss of IgE-bindning1.
Fig 1: This picture shows the trimeric form of the major peanut allergen Ara h1. (PDB ID: 3SMH)
Fig 1: Illustration of the major peanut allergen Ara h1. This picture represents the trimeric form of the protein. (PDB ID: 3SMH)
Fig 2. The first time a B-cell is exposed to Ara h1 no allergic reaction will occure, but plasma cells will initiate an overproduction of IgE antibodies. The IgE molecules attach themselves to mast cells or basophils. The second time Ara h1 enters the body, the IgE antibodies reacts by binding the allergen. The IgE-primed mast cells and basophils will then release granules containing histamine and other allergic mediators. This will cause an allergic reaction.
Fig 2. The first time a B-cell is exposed to Ara h1 no allergic reaction will occure, but plasma cells will initiate an overproduction of IgE antibodies. The IgE molecules attach themselves to mast cells or basophils. When Ara h1 enters the body for the second time, the IgE antibodies reacts by binding the allergen. The IgE-primed mast cells and basophils will then release granules containing histamine and other allergic mediators. This will cause an allergic reaction.
2. PDB. [Updated 2014; cited 2014 October 13]. Available from: http://www.rcsb.org/pdb/explore.do?structureId=3SMH
