Resistance of human betaB2-crystallin to in vivo modification.
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 betaB2-crystallin undergoes less modification than any of the other crystallins. As the lens ages, betaB2-crystallin retains its hydrophilic N-terminus while the hydrophilic C-termini of alpha-crystallins and large portions of the N-termini of betaA3/A1 and betaB1 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 betaB2 than in the other crystallins. This resistance to modification results in higher levels of betaB2 compared with the other crystallins in the water-soluble fraction of older lenses. The solubility of betaB2 and its propensity to form non-covalent associations with less soluble beta-crystallins may contribute to the solubility of the other beta-crystallins. A current hypothesis is that the chaperone-like properties of alpha-crystallins contribute to lens crystallin solubility, particularly in younger lenses. In older lenses, where most of the alpha-crystallins have become water-insoluble, betaB2-crystallins may play a dominant role in lens crystallin solubility.
Zhang
Z
Z
Department of Chemistry, University of Nebraska, Lincoln, NE 68588-0304, USA.
David
L L
LL
Smith
D L
DL
Smith
J B
JB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003459:Crystallins / Q000032:analysis / Q000737:chemistry*; D003641:Deamination; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007908:Lens, Crystalline / Q000737:chemistry*; D008875:Middle Aged; D008970:Molecular Weight; D012995:Solubility; D021241:Spectrometry, Mass, Electrospray Ionization
D003459:Crystallins