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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. As a result, 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:
 [1];  [2];  [3];  [1];  [1];  [4];  [5]
  1. Institute of Food Research, Conley (United Kingdom)
  2. Institute of Food Research, Conley (United Kingdom); Argonne National Lab. (ANL), Argonne, IL (United States)
  3. Institute of Food Research, Conley (United Kingdom); Univ. of Manchester, Manchester (United Kingdom); Univ. of Nebraska-Lincoln, Lincoln, NE (United States)
  4. Univ. of Manchester, Manchester (United Kingdom)
  5. Institute of Food Research, Conley (United Kingdom); Univ. of Manchester, Manchester (United Kingdom)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
Argonne National Laboratory - Argonne Leadership Computing Facility; USDOE
OSTI Identifier:
1332942
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 6; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Abdullah, Syed Umer, Alexeev, Yuri, Johnson, Philip E., Rigby, Neil M., Mackie, Alan R., Dhaliwal, Balvinder, and Mills, E. N. Clare. Ligand binding to an allergenic lipid transfer protein enhances conformational flexibility resulting in an increase in susceptibility to gastroduodenal proteolysis. United States: N. p., 2016. Web. doi:10.1038/srep30279.
Abdullah, Syed Umer, Alexeev, Yuri, Johnson, Philip E., Rigby, Neil M., Mackie, Alan R., Dhaliwal, Balvinder, & Mills, E. N. Clare. Ligand binding to an allergenic lipid transfer protein enhances conformational flexibility resulting in an increase in susceptibility to gastroduodenal proteolysis. United States. https://doi.org/10.1038/srep30279
Abdullah, Syed Umer, Alexeev, Yuri, Johnson, Philip E., Rigby, Neil M., Mackie, Alan R., Dhaliwal, Balvinder, and Mills, E. N. Clare. Tue . "Ligand binding to an allergenic lipid transfer protein enhances conformational flexibility resulting in an increase in susceptibility to gastroduodenal proteolysis". United States. https://doi.org/10.1038/srep30279. https://www.osti.gov/servlets/purl/1332942.
@article{osti_1332942,
title = {Ligand binding to an allergenic lipid transfer protein enhances conformational flexibility resulting in an increase in susceptibility to gastroduodenal proteolysis},
author = {Abdullah, Syed Umer and Alexeev, Yuri and Johnson, Philip E. and Rigby, Neil M. and Mackie, Alan R. and Dhaliwal, Balvinder and Mills, E. N. Clare},
abstractNote = {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. As a result, 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.},
doi = {10.1038/srep30279},
journal = {Scientific Reports},
number = ,
volume = 6,
place = {United States},
year = {Tue Jul 26 00:00:00 EDT 2016},
month = {Tue Jul 26 00:00:00 EDT 2016}
}

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