Food Structure and Health
Protein Structure and Proteolysis
- To characterise the effects of protein scaffold, unfolding and covalent (e.g. Maillard) modifications on the patterns and pathways of GI tract proteolysis using in silico, biophysical and proteomic methods.
Whilst the breakdown of proteins in the gastrointestinal (GI) tract is well understood in general terms, there is a lack of knowledge regarding events at a molecular level. Furthermore, little account has been taken of the complexities introduced by food structure or biomolecular interactions with other components such as lipids found in food or the GI tract itself. One compelling driver to study this is our need to understand why some proteins, and not others, become allergens. Our previous research has shown that food allergens belong to a relatively small number of protein families. We do not understand why this should be, but it may be related to physicochemical properties of these proteins, such as their behaviour during digestion. Whilst doubt has been cast in recent years on the utility of the grossly non-physiological pepsin resistance test for predicting allergenicity, GI processing will modulate the form in which proteins and peptides are transported across the mucosa and presented to the associated immune system.
We propose that a combination of the three dimensional structure of dietary proteins and food structures/components modulate proteolytic pathways in the GI tract. We have a unique, multidisciplinary approach that includes protein biochemistry, proteomics, physical chemistry of food structures, and computer simulation studies to investigate a range of protein structure-function relationships, particularly those underlying protein allergenicity. The research will provide knowledge about the form in which dietary protein may arrive at the gut epithelium for uptake and processing by the immune system and hence affect allergenic potential. We also coordinate a large EU integrated project EuroPREVALL which is characterising the patterns and prevalence of food allergies across Europe, developing methods to improve diagnosis and determining the impact of food allergies on the quality of life and its economic cost.
Our long-term goal is to develop a knowledge-driven computational model of proteolysis that takes account of the influence of a proteins' structure and unfolding and biomolecular interactions with other components. As well as supporting international efforts to predict protein allergenicity in silico, the rules we seek to define will be relevant to studies of intracellular protein turnover in lysosomes and through the cytoplasmic proteosomal pathway. We are investigating this through a combination of molecular modelling and unconventional applications of proteomic technologies. We are using model proteins representing different structural types and behaviours, drawn from the major plant- and animal-derived food allergen families which will include structurally mobile (rheomorphic) proteins such as cow's milk casein, stable β-barrel proteins such as the globulin seed storage proteins (peanut Ara h 1) and Bet v 1 homologues. Others include disulphide-bond stabilised ligand binding proteins such as β-lactoglobulin (β-Lg) and members of the prolamin superfamily (lipid transfer proteins, 2S albumins). Many have well-defined three-dimensional structures which will facilitate our studies.