Aluminum interrupts the formation of alkaline-ribonuclease-inhibitor complex from bovine brain
1Department of Biochemistry, College of Medicine, University of Ulsan, Seoul, Korea.
Insights
Aluminum interferes with alkaline ribonuclease (RNase) binding to its inhibitor in the brain. This interaction may disrupt RNA metabolism regulation, potentially impacting neurological function.
Area of Science:
- Biochemistry
- Neuroscience
- Molecular Biology
Background:
- Alkaline ribonuclease (RNase) plays a role in RNA metabolism.
- RNase activity is regulated by RNase inhibitors.
- Aluminum accumulation in the brain is linked to neurological disorders.
Purpose of the Study:
- To investigate the effect of aluminum on the interaction between alkaline ribonuclease and its inhibitor from bovine brain.
- To elucidate the mechanism by which aluminum affects RNase-inhibitor binding.
Main Methods:
- Purification of alkaline ribonuclease and RNase inhibitor from bovine brain.
- Incubation of RNase with aluminum and assessment of inhibitor binding.
- Stoichiometry determination of aluminum-RNase binding.
- Chemical modification and spectroscopic studies.
- Dialysis experiments to assess aluminum dissociation.
Main Results:
- Aluminum (1:1 stoichiometry) binds to alkaline RNase, but not to the inhibitor.
- Aluminum binding does not abolish RNase activity but prevents inhibitor binding.
- Aluminum-bound RNase-inhibitor complex formation was inhibited.
- Citrate, EDTA, NaF, and apotransferrin protected RNase from aluminum binding.
- Conformational changes induced by aluminum binding to RNase are suggested to hinder inhibitor interaction.
Conclusions:
- Aluminum binding to alkaline RNase disrupts its interaction with RNase inhibitor.
- This disruption may occur through direct competition for binding sites or by inducing conformational changes in the enzyme.
- Aluminum's interference with RNase regulation could impact RNA metabolism in the brain.
Abstract:
The effect of aluminum on alkaline ribonuclease (RNase) and RNase inhibitor, purified from bovine brain, was investigated. Incubation of alkaline RNase with aluminum interrupted binding of RNase inhibitor to alkaline RNase. A stoichiometry of 1:1 for the binding of aluminum to brain alkaline RNase was estimated, whereas no aluminum was found to be bound to the RNase inhibitor. Aluminum-bound alkaline RNase, however, retained a full alkaline RNase activity. None of the enzyme-bound aluminum was dissociated by dialysis against 50 mM Hepes, pH 7.0, at 4 degrees C for 24 h. Citrate, EDTA, NaF and apotransferrin protected the alkaline RNase against aluminum binding. Aluminum did not bind to the incubated alkaline RNase-inhibitor complex, suggesting that aluminum might compete with RNase inhibitor for the binding site. However, the data from chemical modification and spectroscopic studies indicate that it is also highly possible that aluminum binding to the enzyme induces conformational changes at or near the inhibitor-binding site, which subsequently interrupt binding of RNase inhibitor to alkaline RNase. These results suggest that accumulation of aluminum in brain might affect the regulation of RNA metabolism.
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