Post-translational modifications and/or structural changes induced by modifications are likely causes of the decrease in crystallin solubility associated with aging and the development of cataract. Characterization of human lens crystallins by mass spectrometry has demonstrated that βB2-crystallin undergoes less modification than any of the other crystallins. As the lens ages, βB2-crystallin retains its hydrophilic N-terminus while the hydrophilic C-termini of α-crystallins and large portions of the N-termini of βA3/A1 and βB1 are truncated. The hydrophilic terminal regions of crystallins contribute to their solubility. Furthermore, deamidation and disulfide bond formation, other modifications that may affect solubility by altering conformation, are less extensive in βB2 than in the other crystallins. This resistance to modification results in higher levels of βB2 compared with the other crystallins in the water-soluble fraction of older lenses. The solubility of βB2 and its propensity to form non-covalent associations with less soluble β-crystallins may contribute to the solubility of the other β-crystallins. A current hypothesis is that the chaperone-like properties of α-crystallins contribute to lens crystallin solubility, particularly in younger lenses. In older lenses, where most of the α-crystallins have become water-insoluble. βB2-crystallins may play a dominant role in lens crystallin solubility.
- Human lens β-crystallins
- Mass spectrometry
- Post-translational modifications
ASJC Scopus subject areas
- Sensory Systems
- Cellular and Molecular Neuroscience