Publication details for Prof Roy Andrew QuinlanDer Perng, M., Muchowski, P.J., van den IJssel, P., Wu, G.J.S., Hutcheson, A.M., Clark, J.I. & Quinlan, R.A. (1999). The cardiomyopathy and lens cataract mutation in αB-crystallin alters its protein structure, chaperone activity, and interaction withintermediate filaments in vitro. Journal of Biological Chemistry 274(47): 33235-33243.
- Publication type: Journal Article
- ISSN/ISBN: 0021-9258, 1083-351X
- DOI: 10.1074/jbc.274.47.33235
- Further publication details on publisher web site
- Durham Research Online (DRO) - may include full text
Author(s) from Durham
Desmin-related myopathy and cataract are both caused by the R120G mutation in αB-crystallin. Desmin-related myopathy is one of several diseases characterized by the coaggregation of intermediate filaments with αB-crystallin, and it identifies intermediate filaments as important physiological substrates for αB-crystallin. Using recombinant human αB-crystallin, the effects of the disease-causing mutation R120G upon the structure and the chaperone activities of αB-crystallin are reported. The secondary, tertiary, and quaternary structural features of αB-crystallin are all altered by the mutation as deduced by near- and far-UV circular dichroism spectroscopy, size exclusion chromatography, and chymotryptic digestion assays. The R120G αB-crystallin is also less stable than wild type αB-crystallin to heat-induced denaturation. These structural changes coincide with a significant reduction in thein vitro chaperone activity of the mutant αB-crystallin protein, as assessed by temperature-induced protein aggregation assays. The mutation also significantly altered the interaction of αB-crystallin with intermediate filaments. It abolished the ability of αB-crystallin to prevent those filament-filament interactions required to induce gel formation while increasing αB-crystallin binding to assembled intermediate filaments. These activities are closely correlated to the observed disease pathologies characterized by filament aggregation accompanied by αB-crystallin binding. These studies provide important insight into the mechanism of αB-crystallin-induced aggregation of intermediate filaments that causes disease.