Mimicking phosphorylation of αB-crystallin affects its chaperone activity

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dc.contributor.authorEcroyd, H.
dc.contributor.authorMeehan, S.
dc.contributor.authorHorwitz, J.
dc.contributor.authorAquilina, J.
dc.contributor.authorBenesch, J.
dc.contributor.authorRobinson, C.
dc.contributor.authorMacPhee, C.
dc.contributor.authorCarver, J.
dc.date.issued2007
dc.descriptionCopyright © 2007 The Biochemical Society, London
dc.description.abstractαB-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 αB-crystallin. In the present study, we produced recombi-nant proteins designed to mimic phosphorylation of αB-crystallin by incorporating a negative charge at these sites. We employed these mimics to undertake a mechanistic and structural invest-igation of the effect of phosphorylation on the chaperone activity of aB-crystallin to protect against two types of protein misfolding, i.e. amorphous aggregation and amyloid fibril assembly. We show that mimicking phosphorylation of αB-crystallin results in more efficient chaperone activity against both heat-induced and reduc-tion-induced amorphous aggregation of target proteins. Mimick-ing phosphorylation increased the chaperone activity of αB-crystallin against one amyloid-forming target protein (k-casein), but decreased it against another (ccb-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 αB-crystallins. The present study provides evidence for the regulation of the chaperone activity of αB-crystallin by phosphorylation and indicates that this may play an important role in alleviating the pathogenic effects associated with protein conformational diseases.
dc.description.statementofresponsibilityHeath Ecroyd, Sarah Meehan, Joseph Horwitz, J. Andrew Aquilina, Justin L.P. Benesch, Carol V. Robinson, Cait E. MacPhee and John A. Carver
dc.identifier.citationBiochemical Journal, 2007; 401 Part 1(1):129-141
dc.identifier.doi10.1042/BJ20060981
dc.identifier.issn0264-6021
dc.identifier.issn1470-8728
dc.identifier.urihttp://hdl.handle.net/2440/42949
dc.language.isoen
dc.publisherPortland Press
dc.source.urihttps://doi.org/10.1042/bj20060981
dc.titleMimicking phosphorylation of αB-crystallin affects its chaperone activity
dc.title.alternativeMimicking phosphorylation of alphaB-crystallin affects its chaperone activity
dc.typeJournal article
pubs.publication-statusPublished

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