Human beta-crystallins modified by backbone cleavage, deamidation and oxidation are prone to associate.
Information about beta-crystallins and their post-translational modifications has been scarce because of difficulties in isolating the individual beta-crystallins. These difficulties arise because the beta-crystallin sequences are highly homologous and because beta-crystallins undergo many age-related modifications that lead to a variety of molecular masses and a range of acidities for each crystallin. In this study, human beta-crystallins were isolated using several steps of chromatography both before and after two-dimensional gel electrophoresis. Many previously unidentified in vivo modifications, including deamidations among all beta-crystallins except betaB3, truncation of betaA3, betaB1 and betaA4, and oxidation of some methionines and tryptophans were located among the isolated beta-crystallins. Many modifications occurred before age 20 with modest increases in modification for beta-crystallins from lenses 20-87 years old. The tendency of the modified beta-crystallins to form non-covalent complexes was evident from their chromatographic behaviour. The presence in these complexes of betaB2-crystallin, the least modified and most soluble of the beta-crystallins, points to a possible role for betaB2 in solubilizing the more heavily modified beta-crystallins. The greater solubility of beta-crystallins compared with alpha- and gamma-crystallins in aging lenses may be due to beta-crystallin modifications and their non-covalent associations.
Zhang
Zhongli
Z
Department of Chemistry, University of Nebraska, Lincoln, NE 68588-0304, USA.
Smith
David L
DL
Smith
Jean B
JB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003459:Crystallins / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis; D014364:Tryptophan / Q000378:metabolism; D038205:beta-Crystallin A Chain; D038206:beta-Crystallin B Chain / Q000031:analogs & derivatives* / Q000378:metabolism
C103907:CRYBA4 protein, human; C105601:CRYBB1 protein, human; C103908:CRYBB3 protein, human; D003459:Crystallins; D038205:beta-Crystallin A Chain; D038206:beta-Crystallin B Chain; C113634:beta-crystallin B2; D014364:Tryptophan; D008715:Methionine