Mimicking Phosphorylation of Alphab-crystallin Affects Its Chaperone Activity.
From: School of Chemistry and Physics, University of Adelaide, Adelaide, SA 5005, Australia.
The Biochemical journal
- Publish Date: Jan 2007
- ISSN: 1470-8728
- Volume: 401
- Issue: 1
- Pages: 129-41
- Medium: Internet
- Language: English
- Citation (JAMA): Ecroyd Heath, Meehan Sarah, Horwitz Joseph, et al. Mimicking Phosphorylation of Alphab-crystallin Affects Its Chaperone Activity.. Biochem. J. Jan 2007;401:129-41
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.
Mesh Headings (Keywords): Animals, Caseins, Catalase, Cattle, Female, Lactalbumin, Liver, Milk, Molecular Chaperones, Nephelometry and Turbidimetry, Phosphorylation, Scattering, Radiation, alpha-Crystallin B Chain
Check for Full Text / PubMed Unique Identifier (PMID): 16928191
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