Structural insight into protein T1, the non-allergenic member of the Bet v 1 allergen family-An in silico analysis.
BACKGROUND
Bet v 1 family is a large group of allergens present in pollen and plant-derived foods. They show similarity in sequence and 3D structure, properties often correlated to their cross-reactivity. protein T1 is a naturally occurring non-allergenic member of this group, which, in spite of having 35-85% sequence similarity, does not exhibit antibody-mediated cross-reactivity with other members of the Bet v 1 allergen family. This protein has been suggested to be a good model to study structural features critically needed for allergenicity and cross-reactivity.


OBJECTIVE
Structural bioinformatic approach to analyze the properties of protein T1 in relation to allergenicity and cross-reactivity.


METHODS
A 3D model of protein T1 was constructed by the homology modeling procedure and was compared to the structure of Bet v 1 with special reference to conservation, solvent accessibility and electrostatic properties of the residues across the antigenic surface.


RESULTS
The over-all fold of the homology model of T1 resembles that of the Bet v 1 group. The change in the solvent-accessible surface of the IgG (BV16)-binding residues has been quantified to be 75%. Comparing the allergenically potent dimer structure of Bet v 1 (predicted structure available in MSD of European Bioinformatics Institute), with the non-allergenic monomer, the BV16-binding surface and the p-loop seem to be of less importance for Bet v 1-mediated in vivo cross-linking of IgE. Instead, we think that other surface-exposed conserved patches are more significant. Absence of cross-reactivity between T1 and Bet v 1 comes from the lack of surface conservation leading to changes in the conformational as well as electrostatic properties. On the other hand, certain changes in the sequence, that might hinder dimerization of this protein, may result in the loss of allergenicity. Lastly, our structural docking experiment shows that protein T1 can bind two molecules of Brassinolide ligands like the other members of the Bet v 1 family.


CONCLUSIONS
Lack of dimerization and surface conservation might explain the reason why T1 is neither allergenic, nor cross-reactive to Bet v 1 group, although this protein can be a potential carrier for brassinosteroids.
Department of Botany, Bose Institute, 93/1 A.P.C Road, Kolkata 700009, India.
Debajyoti
D
Ghosh
Swati
S
Gupta-Bhattacharya
D000485:Allergens / Q000737:chemistry*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D060406:Brassinosteroids; D002777:Cholestanols / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D003429:Cross Reactions; D019281:Dimerization; D000939:Epitopes / Q000737:chemistry; D007136:Immunoglobulins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D013260:Steroids, Heterocyclic / Q000378:metabolism; D040681:Structural Homology, Protein
D000485:Allergens; D000596:Amino Acids; D060406:Brassinosteroids; D002777:Cholestanols; D000939:Epitopes; D007136:Immunoglobulins; D010940:Plant Proteins; D013260:Steroids, Heterocyclic; C023623:brassinolide