An Atypical Form of αB-crystallin Is Present in High Concentration in Some Human Cataractous Lenses IDENTIFICATION AND CHARACTERIZATION OF ABERRANT N- AND C-TERMINAL PROCESSING

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 αBg was comparable to that of recombinant human αB-crystallin in preventing the aggregation of lactalbumin induced by dithiothreitol. The mechanism involved in generating αBg 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 αBg. The 16.4-kDa protein was an N-terminally truncated fragment of αBg. The high concentration of αB-crystallin in these cataracts is the first observation of this kind in human lenses