Resistance of human beta B2-crystallin to in vivo modification

Post-translational modifications and/or structural changes induced by modif ications are likely causes of the decrease in crystallin solubility associa ted with aging and the development of cataract. Characterization of human l ens crystallins by mass spectrometry has demonstrated that beta B2-crystall in undergoes less modification than any of the other crystallins. As the le ns ages, beta B2-crystallin retains its hydrophilic N-terminus while the hy drophilic C-termini of alpha -crystallins and large portions of the N-termi ni of beta A3/A1 and beta B1 are truncated. The hydrophilic terminal region s of crystallins contribute to their solubility, Furthermore, deamidation a nd disulfide bond formation, other modifications that may affect solubility by altering conformation, are less extensive in beta B2 than in the other crystallins, This resistance to modification results in higher levels of be ta B2 compared with the other crystallins in the water-soluble fraction of older lenses. The solubility of beta B2 and its propensity to form non-cova lent associations with less soluble beta -crystallins may contribute to the solubility of the other beta -crystallins. A current hypothesis is that th e chaperone-like properties of alpha -crystallins contribute to lens crysta llin solubility, particularly in younger lenses. In older lenses, where mos t of the alpha -crystallins have become water-insoluble, beta B2-crystallin s may play a dominant role in lens crystallin solubility. (C) 2001 Academic Press.