Role of cysteine residues in the enhancement of chaperone function in methylglyoxal-modified human αA-crystallin

Abstract

We have previously demonstrated that the reaction of a physiological dicarbonyl, methylglyoxal (MGO) enhances the chaperone function of human αA-crystallin. MGO can react with cysteine, arginine, and lysine residues in proteins. Although the role of arginine and lysine residues in the enhancement of chaperone function has been investigated, the role of cysteine residues is yet to be determined. In this study, we have investigated the effect of MGO modification on the structure and chaperone function of αA-crystallin mutant proteins in which C131 and C142 were replaced either individually or simultaneously with isoleucine. MGO-modification resulted in improved chaperone function in all three αA-crystallin mutants, including the cysteine-free double mutant. The enhanced chaperone function was due to increased surface hydrophobicity and increased binding of client proteins. These results suggest that the two cysteine residues, even though they could be modified, do not take part in the MGO-induced improvement in the chaperone function of human αA-crystallin.

The role of the cysteine residue in the chaperone and anti‐apoptotic functions of human Hsp27

“…However, the present results differ from those from a previous study, which revealed that cysteine mutation in the related αA-crystallin, the replacement of C131 or C142 with an isoleucine, brought about a profound reduction in the chaperone function of the protein [Kanade et al, 2009]. This suggests that Hsp27 does not interact with its client proteins at its cysteine residue unlike αA-crystallin, which is likely to interact with client proteins at its two cysteine residues.…”

Energy metabolism, proteotoxic stress and age-related dysfunction – Protection by carnosine

“…Furthermore, preconditioning with AGEs may also upregulate the anti-oxidant activity of cardiac cells (Ruhs et al, 2010). Other studies have shown that the activity of certain stress proteins can be increased following their reaction with MG (Kanade et al, 2009).…”

Lens aging: Effects of crystallins

“…Methylglyoxal reacts with Arg, Cys and Lys to produce stable adducts and cross-links and is one of the glycating dicarbonyls in the lens [83, 109, 113, 125]. It has been shown that Cys residues in aA-crystallin are not involved in methylglyoxal-mediated enhancement of chaperone activity [126]. The neutralization of the positive charge on Arg by methylglyoxal is apparently responsible for the enhanced chaperone activity of a-crystallin [127].…”