An atypical form of αB-crystallin is present in high concentration in some human cataractous lenses

Abstract

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 αBg. Mass spectrometric analyses of tryptic and Asp-N digests showed αBg is αB-crystallin minus the C-terminal lysine. αBg constituted 10–90% of the total αB-crystallin in these cataracts and was preferentially phosphorylated over the typical form of αB-crystallin. Human αBg and αB-crystallin were cloned and expressed inEscherichia 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.