Effect of methylglyoxal modification on stress-induced aggregation of client proteins and their chaperoning by human αA-crystallin

alpha-Crystallin prevents protein aggregation under various stress conditions through its chaperone-like properties. Previously, we demonstrated that MGO (methylglyoxal) modification of alpha A-crystallin enhances its chaperone function and thus may affect transparency of the lens. During aging of the lens, not only alpha A-crystallin, but its client proteins are also likely to be modified by MGO. We have investigated the role of MGO modification of four model client proteins (insulin, alpha-lactalbumin, alcohol dehydrogenase and gamma-crystallin) in their aggregation and structure and the ability of human alpha A-crystallin to chaperone them. We found that MGO modification (10-1000 mu M) decreased the chemical aggregation of insulin and alpha-lactalbumin and thermal aggregation of alcohol dehydrogenase and gamma-crystallin. Surface hydrophobicity in MGO-modified proteins decreased slightly relative to unmodified proteins. HPLC and MS analyses revealed argpyrimidine and hydroimidazolone in MGO-modified client proteins. The degree of chaperoning by alpha A-crystallin towards MGO-modified and unmodified client proteins was similar. Co-modification of client proteins and alpha A-crystallin by MGO completely inhibited stress-induced aggregation of client proteins. Our results indicate that minor modifications of client proteins and alpha A-crystallin by MGO might prevent protein aggregation and thus help maintain transparency of the aging lens.