School Of Basic And Applied Sciences
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Item Specific Genetic Polymorphisms Contributing in Differential Binding of Gliadin Peptides to HLA-DQ and TCR to Elicit Immunogenicity in Celiac Disease(Springer, 2023-04-27T00:00:00) Banerjee, Pratibha; Chaudhary, Ramprasad; Singh, Atul Kumar; Parulekar, Pratima; Kumar, Shashank; Senapati, SabyasachiImmunogenicity of gliadin peptides in celiac disease (CD)�is majorly determined by the pattern of molecular interactions with HLA-DQ and T-cell receptors (TCR). Investigation of the interactions between immune-dominant gliadin peptides, DQ protein, and TCR are warranted to unravel the basis of immunogenicity and variability contributed by the genetic polymorphisms. Homology modeling of HLA and TCR done using Swiss Model and iTASSER, respectively. Molecular interactions of eight common deamidated immune-dominant gliadin with HLA-DQ allotypes and specific TCR gene pairs were evaluated. Docking of the three structures was performed with ClusPro2.0 and ProDiGY was used to predict binding energies. Effects of known allelic polymorphisms and reported susceptibility SNPs were predicted on protein�protein interactions. CD susceptible allele, HLA-DQ2.5 was shown to have considerable binding affinity to 33-mer gliadin (?G = ?�13.9; Kd = 1.5E�?�10) in the presence of TRAV26/TRBV7. Higher binding affinity was predicted (?G = ?�14.3, Kd = 8.9E�?�11) when TRBV28 was replaced with TRBV20 paired with TRAV4 suggesting its role in CD predisposition. SNP rs12722069 at HLA-DQ8 that codes Arg76? forms three H-bonds with Glu12 and two H-bonds with Asn13 of DQ2 restricted gliadin in the presence of TRAV8-3/TRBV6. None of the HLA-DQ polymorphisms was found to be in linkage disequilibrium with reported CD susceptibility markers. Haplotypic presentations of rs12722069-G, rs1130392-C, rs3188043-C and rs4193-A with CD reported SNPs were observed in sub-ethnic groups. Highly polymorphic sites of HLA alleles and TCR variable regions could be utilized for better risk prediction models in CD. Therapeutic strategies by identifying inhibitors or blockers targeting specific gliadin:HLA-DQ:TCR binding sites could be investigated. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Characterization of Hexaploid Wheat Protein on the Basis of their Date of Release in Indian sub- continent(Central University of Punjab, 2018) Negi, Arti; Dhiman MonishaWheat is the third most grown cereal worldwide. The storage proteins of wheat represent an important source of food and energy and are also involved in the determination of bread wheat quality. These gluten proteins are categorized as prolamins, composed of monomeric gliadin (single chain polypeptides) and polymeric glutenin (multiple polypeptide chains).Unfortunately consumption of these gluten protein is known to be linked with range of clinical disorders e.g. celiac disease, wheat allergy and wheat intolerance. The main objective of the present work is to elaborate a detailed knowledge of the variability of proteins and protein fractions of the wheat varieties based on their origin. 25 wheat varieties procured from Indian Institute of Wheat and Barley Research were evaluated for analysis of total wheat protein and gluten protein by sodium dodecyl sulfate- polyacrylamide gel electrophoresis (SDS- PAGE) and cluster analysis was done based on SDS-PAGE gels to investigate variation among varieties. Multiple sequence alignment of ?-gliadin protein of different genes was done and region of highest variability among them is reported. This study shows that 25 varieties of wheat of different origin vary in their total wheat protein as well as gluten content. However the results of cluster analysis of gluten showed low degree of heterogeneity among the varieties.