Authors: Rajshekhar Kore Rebecca A Hedges Lalita Oonthonpan Puttur Santhoshkumar Krishna K Sharma Edathara C Abraham
Publish Date: 2011/11/02
Volume: 362, Issue: 1-2, Pages: 93-102
Abstract
Pediatric cataract of the congenital type is the most common form of childhood blindness and it is clinically and genetically heterogeneous Mutations in 22 different genes have been identified to be associated with congenital cataracts and among them eight mutants belong to αAcrystallin To explain how mutations in αAcrystallin lead to the development of cataract quaternary structural parameters and chaperone function have been investigated in αAwt and in the following mutants R12C R21L R21W R49C R54C R116C and R116H Average molar mass mass at the RI peak mass across the peak hydrodynamic radius R h and polydispersity index PDI were determined by dynamic lightscattering measurements The average molar mass and mass across the peak showed major increase in R116C and R116H moderate increase in R12C R21W and R54C and no increase in R21L and R49C as compared to αAwt PDI and R h values were significantly increased only in R116C and R116H Significant secondary structural changes as determined by CD measurements were seen in R21W R21L R116C and R116H and tertiary structural changes were evident in R21W R54C R116C and R116H Nonreducing SDSPAGE has shown the presence of dimers presumably formed by interpolypeptide disulfide bonds Chaperone activity as measured with ADH as the target protein appeared normal in R49C and R54C while R12C R21L and R21W showed moderate loss and R116C and R116H showed significant loss Although a specific change in the αAcrystallin behavior that is common to all the mutants was not evident each mutant showed one or more perturbation as the end effect that leads to cataract
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