Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 375, Issue 4, Pages 1040-1051Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2007.11.019
Keywords
alpha B-crystallin; phosphorylation-mimic; mixed oligomers; chaperone; aggregation
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Phosphorylation appears to be one of the modulators of chaperone functions of small heat shock proteins. However, the role of phosphorylation is not completely understood. We have investigated the structural and functional consequences of a phosphorylation-mimicking mutation in alpha B-crystallin, a small heat shock protein with chaperone activity. We have used a phosphorylation-mimicking mutant, 3D alpha B-crystallin, in which all the three phosphorylatable serine residues are replaced with aspartic acid. 3D alpha B-Crystallin showed enhanced chaperone-like activity towards DTT-induced aggregation of insulin, heat-induced aggregation of citrate synthase and SDS-induced amyloid fibril formation of alpha-synuclein. Fluorescence and circular dichroism spectroscopic studies showed that 3D alpha B-crystallin exhibits lower stability towards urea-induced denaturation compared to alpha B-crystallin. Subunit exchange studies using fluorescence resonance energy transfer showed that 3D alpha B-crystallin exhibits an observable increase in subunit exchange compared to alpha B-crystallin. Since only part of alpha B-crystallin is phosphorylated in vivo, our subunit exchange studies indicate that formation of mixed oligomers between the unphosphorylated and phosphorylated subunits are likely to play a role in vivo. Our study shows that mixed-oligomer formation modulates the chaperone-like activity. We propose that the degree of phosphorylation of the alpha B-crystallin oligomers and temperature are key modulators to achieve a wide range of chaperone capabilities of the small heat shock protein, alpha B-crystallin. (c) 2007 Elsevier Ltd. All rights reserved.
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