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The cardiomyopathy and lens cataract mutation in αB-crystallin alters its protein structure, chaperone activity, and interaction withintermediate filaments in vitro.

Der Perng, M. and Muchowski, P.J. and van den IJssel, P. and Wu, G.J.S. and Hutcheson, A.M. and Clark, J.I. and 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). pp. 33235-33243.

Abstract

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.

Item Type:Article
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Status:Peer-reviewed
Publisher Web site:https://doi.org/10.1074/jbc.274.47.33235
Publisher statement:This research was originally published in The Journal of Biological Chemistry. Ming Der Perng, Paul J. Muchowski, Paul van den IJssel, Gabrielle J. S. Wu, Aileen M. Hutcheson, John I. Clark, and Roy A. Quinlan. The Cardiomyopathy and Lens Cataract Mutation in αB-crystallin Alters Its Protein Structure, Chaperone Activity, and Interaction with Intermediate Filaments in Vitro. The Journal of Biological Chemistry. 1999. 274: 33235-33243. © the American Society for Biochemistry and Molecular Biology
Date accepted:No date available
Date deposited:20 December 2017
Date of first online publication:19 November 1999
Date first made open access:No date available

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