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High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
Manganese binding to the prion protein.
Marcus W Brazier1, Paul Davies, Esmie Player
1Department of Biology and Biochemistry and Chemistry, University of Bath, Bath BA2 7AY, UK.
The Journal of Biological Chemistry
|March 12, 2008
Summary
Prion protein (PrP) binds manganese, similar to copper. Manganese binding alters PrP conformation, potentially triggering changes linked to prion disease.
Area of Science:
- Biochemistry
- Neuroscience
- Protein Chemistry
Background:
- Prion protein (PrP) is known to bind copper.
- Emerging evidence suggests PrP may also bind manganese.
- Understanding metal-protein interactions is crucial for prion disease research.
Purpose of the Study:
- To identify manganese binding sites in wild-type mouse PrP.
- To characterize the biophysical and chemical consequences of manganese binding to PrP.
- To investigate the potential role of manganese in PrP conformational changes.
Main Methods:
- Isothermal titration calorimetry (ITC) to determine manganese binding affinities and sites.
- Cyclic voltammetry to analyze the redox chemistry of metal-PrP complexes.
- Conformational change assays to assess PrP aggregation.
Main Results:
- PrP exhibits two manganese binding sites with significant affinity at physiological pH.
- The primary manganese binding site involves His-95, overlapping with a known copper binding site.
- Manganese binding alters PrP conformation, displaces copper, and changes the protein's redox properties.
- Manganese-bound PrP catalyzes the aggregation of metal-free PrP, mimicking disease-associated changes.
Conclusions:
- PrP binds manganese with affinities comparable to other manganese-binding proteins.
- Manganese binding induces significant structural and functional alterations in PrP.
- These manganese-induced changes in PrP may contribute to the pathogenesis of prion diseases.
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