IERG Abstracrt Book.indd - LV Prasad Eye Institute

Basic Poster Sessions77Results: Distribution of the GC genotype for rs1800471 (Arg25Pro) showed significantdifference between the cases and controls with a p value of 0.0002 (OR 0.219 and 95%CI).THESIAS analysis revealed significant association for the C-C haplotype (Pro-Pro) with axiallength (p= 0.0239). Signal P analysis revealed altered peptide cleavage score for the C-Chaplotype suggesting a possible effect on TGF beta expression. However rs1800470 (Leu10Pro) was not statistically significant.Conclusions: In this study, distribution of the GC genotype of rs1800471 showed significantassociation with myopia. The C-C haplotype (10P25P) was shown to have interaction with axiallength and needs further validation by functional studies.IBP 028Differential Regulation of Ca2+-binding to Structurally Similar bg-CrystallinsShashi Kumar Suman, Amita Mishra, Yogendra SharmaCentre for Cellular and Molecular Biology, Hyderabad, IndiaPurpose: beta- and gamma-crystallins are the major components of eye lens. Structuralhomologues are found in some lower eukaryotes and prokaryotes and together form abg-crystallin superfamily. Numerous members of the bg-crystallin superfamily bind Ca2+at the double-clamp motif with a consensus sequence of N/D-N/D-X1-X2-S/T-S. However,certain details such as the determinants of Ca2+-induced gain in stability and affinity are notunderstood.Methods: To investigate these features and the basis of moderate or high affinity of thecanonical motif in the superfamily, we performed extensive but calculated mutations in the sixresidues of Ca2+-binding site on two bg-crystallin domains that are structurally similar butdiffer in Ca2+-binding properties.Results: Replacement of Ser by Thr has dramatic effects on the Ca2+-binding affinity, due toalteration in the local environment by the methyl group of Thr. Replacing Thr by Ser eitherdecreases the Ca2+-binding affinity partially or has no influence (depending on the bindingsite). However, these proteins confer significant growth advantage to bacteria compared toits wild-type protein. The polarity or hydrophobicity of X1 residue in the N/DN/DX1X2S/TS motif is highly variable and affects the Ca2+-induced gain in thermal stability (via entropicstabilization or destabilization) significantly. If X1 residue is polar, Ca2+ is unlikely to induce anygain in thermal stability (and confers growth disadvantage to E. coli), whereas a hydrophobicresidue is linked with the gain of significantly high thermal stability by Ca2+ (and conferssignificant growth advantage).Conclusions: Our study demonstrates how the nature of a particular amino acid and microenvironmentalfactors around binding site govern the Ca2+-binding properties of bg-crystallinsand confers growth advantage or disadvantage, thus provides the functional diversity to thedomain despite structural similarities. This diversity in Ca2+-binding properties providesdifferential yet unknown functions in the organisms. Additionally, it is possible that any mutationin this region in lens crystallins would be directly linked with cataract.