Mimicking phosphorylation of alphaB-crystallin affects its chaperone activity.

Ecroyd, H; Meehan, S; Horwitz, J; Aquilina, J; Benesch, J; Robinson, C; Macphee, C; Carver, J

Journal article

Mimicking phosphorylation of alphaB-crystallin affects its chaperone activity.

Abstract:: AlphaB-crystallin is a member of the sHsp (small heat-shock protein) family that prevents misfolded target proteins from aggregating and precipitating. Phosphorylation at three serine residues (Ser19, Ser45 and Ser59) is a major post-translational modification that occurs to alphaB-crystallin. In the present study, we produced recombinant proteins designed to mimic phosphorylation of alphaB-crystallin by incorporating a negative charge at these sites. We employed these mimics to undertake a mechanistic and structural investigation of the effect of phosphorylation on the chaperone activity of alphaB-crystallin to protect against two types of protein misfolding, i.e. amorphous aggregation and amyloid fibril assembly. We show that mimicking phosphorylation of alphaB-crystallin results in more efficient chaperone activity against both heat-induced and reduction-induced amorphous aggregation of target proteins. Mimick-ing phosphorylation increased the chaperone activity of alphaB-crystallin against one amyloid-forming target protein (kappa-casein), but decreased it against another (ccbeta-Trp peptide). We observed that both target protein identity and solution (buffer) conditions are critical factors in determining the relative chaperone ability of wild-type and phosphorylated alphaB-crystallins. The present study provides evidence for the regulation of the chaperone activity of alphaB-crystallin by phosphorylation and indicates that this may play an important role in alleviating the pathogenic effects associated with protein conformational diseases.

Publication status:: Published

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APA Style

Ecroyd, H., Meehan, S., Horwitz, J., Aquilina, J., Benesch, J., Robinson, C., Macphee, C., & Carver, J. (2007). Mimicking phosphorylation of alphaB-crystallin affects its chaperone activity. Biochemical Journal, 401(1), 129–141.

MLA Style

Ecroyd, H., et al. “Mimicking Phosphorylation of AlphaB-Crystallin Affects Its Chaperone Activity.” Biochemical Journal, vol. 401, no. 1, 2007, pp. 129–41.

Chicago Style

Ecroyd, H, S Meehan, J Horwitz, J Aquilina, J Benesch, C Robinson, C Macphee, and J Carver. 2007. “Mimicking Phosphorylation of AlphaB-Crystallin Affects Its Chaperone Activity.” Biochemical Journal 401 (1): 129–41.
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