title: Ligand binding to an Allergenic Lipid Transfer Protein Enhances Conformational Flexibility resulting in an Increase in Susceptibility to Gastroduodenal Proteolysis.
abstract: Non-specific lipid transfer proteins (LTPs) are a family of lipid-binding molecules that are widely distributed across flowering plant species, many of which have been identified as allergens. They are highly resistant to simulated gastroduodenal proteolysis, a property that may play a role in determining their allergenicity and it has been suggested that lipid binding may further increase stability to proteolysis. It is demonstrated that LTPs from wheat and peach bind a range of lipids in a variety of conditions, including those found in the gastroduodenal tract. Both LTPs are initially cleaved during gastroduodenal proteolysis at three major sites between residues 39-40, 56-57 and 79-80, with wheat LTP being more resistant to cleavage than its peach ortholog. The susceptibility of wheat LTP to proteolyic cleavage increases significantly upon lipid binding. This enhanced digestibility is likely to be due to the displacement of Tyr79 and surrounding residues from the internal hydrophobic cavity upon ligand binding to the solvent exposed exterior of the LTP, facilitating proteolysis. Such knowledge contributes to our understanding as to how resistance to digestion can be used in allergenicity risk assessment of novel food proteins, including GMOs.
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, NR4 7UA, UK.
authors.forename: Syed Umer
authors.initials: SU
authors.lastname: Abdullah
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, NR4 7UA, UK.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Alexeev
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, NR4 7UA, UK.|Institute of Inflammation and Repair, Manchester Academic Health Sciences Centre and Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Johnson
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, NR4 7UA, UK.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Rigby
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, NR4 7UA, UK.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Mackie
authors.affiliation: Institute of Inflammation and Repair, Manchester Academic Health Sciences Centre and Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: Balvinder
authors.initials: B
authors.lastname: Dhaliwal
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, NR4 7UA, UK.|Institute of Inflammation and Repair, Manchester Academic Health Sciences Centre and Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: E N Clare
authors.initials: ENC
authors.lastname: Mills
mesh_terms: D000485:Allergens / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology*; D000595:Amino Acid Sequence; D052179:Antigens, Plant / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology*; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology*; D005512:Food Hypersensitivity / Q000276:immunology; D041981:Gastrointestinal Tract / Q000737:chemistry / Q000276:immunology; D057927:Hydrophobic and Hydrophilic Interactions; D007073:Immunoglobulin E / Q000276:immunology; D008024:Ligands; D008055:Lipids / Q000737:chemistry / Q000276:immunology*; D030821:Plants, Genetically Modified / Q000009:adverse effects / Q000276:immunology; D059748:Proteolysis; D000068239:Prunus persica / Q000737:chemistry / Q000276:immunology; D014908:Triticum / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D002352:Carrier Proteins; D008024:Ligands; D008055:Lipids; C030363:lipid transfer protein; D007073:Immunoglobulin E