The conformation formed by the domain after alanine-155 induces inversion of aspartic acid-151 in alpha A-crystallin from aged human lenses

A new cleavage site, which is a post-translational modification, was found between residues His-154 and Ala-155 in alpha A-crystallin hom the aged human lens. After trypsin digestion of alpha A-crystallin two peptides that include Asp-151 were obtained and have remarkable differences. That is, the stereo-configuration of the Asp-151 in the normal length peptide was predominately inverted to the D-isomer of beta-aspartyl form (D/L of 5.7), However, the stereoconfiguration of the Asp-151 in the cleavage peptide, that lacks the sequence following Ala-155 to the C-terminus, remained predominately in the L-isomer form as indicated by a D/L value of 0.3. The results suggest that the secondary structure in the region of Ala-155 to the C-terminus may constitute a held that causes the inversion of the Asp-151 to the D-isomer form, Since this kind of cleavage was not found in alpha A-crystallin from young lens, the cleavage between His-154 and Ala-155 is probably the result of aging. (C) 1997 Academic Press.