IN-VIVO ACETYLATION IDENTIFIED AT LYSINE-70 OF HUMAN LENS ALPHA-A-CRYSTALLIN

Posttranslational modification of protein lysyl. residues that change the net charge of the molecule may alter the protein conformation. Suc h modifications are of particular significance among lens proteins, be cause conformational changes are associated with the development of ca taract. A previously unidentified acetylated form of alpha A-crystalli n has been isolated from the water-soluble portion of human lenses. Th e alpha A-crystallins were fractionated by anion exchange HPLC into se ven peaks, each containing more than one form of alpha A-crystallin, T he previously reported deamidated and phosphorylated forms were identi fied by their molecular masses, determined by electrospray ionization mass spectrometry. In addition to these modifications, approximately 5 % of alpha A-crystallin had a modification that decreased the charge b y one and increased the molecular mass by 42 u. This modification, ide ntified as acetylation, was located uniquely at Lys 70. Like any modif ication that alters the surface charge, acetylation may affect protein conformation and intermolecular interactions, thereby altering the so lubility or chaperone properties of alpha A-crystallin, Acetylation of lysine 70 is potentially significant since it is located in a region that has been implicated in the chaperone activity of alpha A-crystall in.