An Atypical Form of αB-crystallin Is Present in High Concentration in Some Human Cataractous Lenses

Two unique polypeptides, 22.4 and 16.4 kDa, were prominent in some human cataracts. Both proteins were identified as modified forms of the small heat shock protein, αB-crystallin. The concentration of total αB-crystallin in most of these cataracts was significantly increased. The 22.4-kDa protein was subsequently designated as αB g . Mass spectrometric analyses of tryptic and Asp-N digests showed αB g is αB-crystallin minus the C-terminal lysine. αB g constituted 10–90% of the total αB-crystallin in these cataracts and was preferentially phosphorylated over the typical form of αB-crystallin. Human αB g and αB-crystallin were cloned and expressed in Escherichia coli . The differences in electrophoretic mobility and the large difference in native pI values suggest some structural differences exist. The chaperone-like activity of recombinant human αB g was comparable to that of recombinant human αB-crystallin in preventing the aggregation of lactalbumin induced by dithiothreitol. The mechanism involved in generating αB g is not known, but a premature termination of the αB-crystallin gene was ruled out by sequencing the polymerase chain reaction products of the last exon for the αB-crystallin gene from lenses containing αB g . The 16.4-kDa protein was an N-terminally truncated fragment of αB g . The high concentration of αB-crystallin in these cataracts is the first observation of this kind in human lenses.