Interaction of human recombinant alphaA- and alphaB-crystallins with early and late unfolding intermediates of citrate synthase on its thermal denaturation.

We have investigated the role of recombinant human alphaA- and alphaB-crystallins in the heat-induced inactivation and aggregation of citrate synthase. Homo-multimers of both alphaA- and alphaB-crystallins confer protection against heat-induced inactivation in a concentration-dependent manner and also prevent aggregation. Interaction of crystallins with early unfolding intermediates of citrate synthase reduces ...
their partitioning into aggregation-prone intermediates. This appears to result in enhanced population of early unfolding intermediates that can be reactivated by its substrate, oxaloacetate. Both these homo-multimers do not form a stable complex with the early unfolding intermediates. However, they can form a soluble, stable complex with aggregation-prone late unfolding intermediates. This soluble complex formation prevents aggregation. Thus, it appears that the chaperone activity of alpha-crystallin involves both transient and stable interactions depending on the nature of intermediates on the unfolding pathway; one leads to reactivation of the enzyme activity while the other prevents aggregation.
Mesh Terms:
Chromatography, Gel, Citrate (si)-Synthase, Crystallins, Dose-Response Relationship, Drug, Enzyme Stability, Hot Temperature, Humans, Macromolecular Substances, Molecular Chaperones, Oxaloacetate, Protein Binding, Protein Denaturation, Protein Folding, Recombinant Proteins
FEBS Lett.
Date: May. 25, 2001
Download Curated Data For This Publication
2038
Switch View:
  • Interactions 1