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The small heat-shock protein αB-crystallin uses different mechanisms of chaperone action to prevent the amorphous versus fibrillar aggregation of α-lactalbumin

Journal Article


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Abstract


  • Stress conditions can destabilize proteins, promoting them to unfold and adopt intermediately folded states. Partially folded protein intermediates are unstable and prone to aggregation down off-folding pathways leading to the formation of either amorphous or amyloid fibril aggregates. The sHsp (small heat-shock protein) αB-crystallin acts as a molecular chaperone to prevent both amorphous and fibrillar protein aggregation; however, the precise molecular mechanisms behind its chaperone action are incompletely understood. To investigate whether the chaperone activity of αB-crystallin is dependent upon the form of aggregation (amorphous compared with fibrillar), bovine α-lactalbumin was developed as a model target protein that could be induced to aggregate down either off-folding pathway using comparable buffer conditions. Thus when α-lactalbumin was reduced it aggregated amorphously, whereas a reduced and carboxymethylated form aggregated to form amyloid fibrils. Using this model, αB-crystallin was shown to be a more efficient chaperone against amorphously aggregating α-lactalbumin than when it aggregated to form fibrils. Moreover, αB-crystallin forms high molecular mass complexes with α-lactalbumin to prevent its amorphous aggregation, but prevents fibril formation via weak transient interactions. Thus, the conformational stability of the protein intermediate, which is a precursor to aggregation, plays a critical role in modulating the chaperone mechanism of αB-crystallin.

Publication Date


  • 2012

Citation


  • Kulig, M. & Ecroyd, H. (2012). The small heat-shock protein αB-crystallin uses different mechanisms of chaperone action to prevent the amorphous versus fibrillar aggregation of α-lactalbumin. Biochemical Journal, 448 (3), 343-352.

Scopus Eid


  • 2-s2.0-84870015466

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1068&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/69

Has Global Citation Frequency


Number Of Pages


  • 9

Start Page


  • 343

End Page


  • 352

Volume


  • 448

Issue


  • 3

Place Of Publication


  • United Kingdom

Abstract


  • Stress conditions can destabilize proteins, promoting them to unfold and adopt intermediately folded states. Partially folded protein intermediates are unstable and prone to aggregation down off-folding pathways leading to the formation of either amorphous or amyloid fibril aggregates. The sHsp (small heat-shock protein) αB-crystallin acts as a molecular chaperone to prevent both amorphous and fibrillar protein aggregation; however, the precise molecular mechanisms behind its chaperone action are incompletely understood. To investigate whether the chaperone activity of αB-crystallin is dependent upon the form of aggregation (amorphous compared with fibrillar), bovine α-lactalbumin was developed as a model target protein that could be induced to aggregate down either off-folding pathway using comparable buffer conditions. Thus when α-lactalbumin was reduced it aggregated amorphously, whereas a reduced and carboxymethylated form aggregated to form amyloid fibrils. Using this model, αB-crystallin was shown to be a more efficient chaperone against amorphously aggregating α-lactalbumin than when it aggregated to form fibrils. Moreover, αB-crystallin forms high molecular mass complexes with α-lactalbumin to prevent its amorphous aggregation, but prevents fibril formation via weak transient interactions. Thus, the conformational stability of the protein intermediate, which is a precursor to aggregation, plays a critical role in modulating the chaperone mechanism of αB-crystallin.

Publication Date


  • 2012

Citation


  • Kulig, M. & Ecroyd, H. (2012). The small heat-shock protein αB-crystallin uses different mechanisms of chaperone action to prevent the amorphous versus fibrillar aggregation of α-lactalbumin. Biochemical Journal, 448 (3), 343-352.

Scopus Eid


  • 2-s2.0-84870015466

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1068&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/69

Has Global Citation Frequency


Number Of Pages


  • 9

Start Page


  • 343

End Page


  • 352

Volume


  • 448

Issue


  • 3

Place Of Publication


  • United Kingdom