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07:08
Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
Post-aggregation oxidation of mutant huntingtin controls the interactions between aggregates
Yasushi Mitomi1, Takao Nomura, Masaru Kurosawa
1Laboratory for Mechanistic Chemistry of Biomolecules, Department of Chemistry, Keio University, Yokohama, Kanagawa 223-8522, Japan.
The Journal of Biological Chemistry
|August 15, 2012
Summary
Protein aggregates, like those in Huntington disease, can be oxidized after formation. This post-aggregation oxidation of huntingtin (HTT) alters aggregate structure and interactions, revealing a new regulatory mechanism.
Area of Science:
- Biochemistry
- Neuroscience
- Molecular Biology
Background:
- Protein aggregation is central to neurodegenerative diseases.
- Post-translational modifications influence protein aggregation.
- The timing of modifications during aggregation is largely unknown.
Purpose of the Study:
- To investigate the timing of protein modifications during aggregation.
- To examine methionine oxidation in huntingtin (HTT) aggregation.
- To determine if oxidation occurs in soluble or aggregated HTT.
Main Methods:
- In vitro and in vivo studies of huntingtin (HTT) aggregation.
- Induction of methionine oxidation using copper ions and hydrogen peroxide.
- Analysis of HTT aggregate morphology and interactions.
Main Results:
- Methionine residue oxidation was observed in aggregated HTT, not soluble HTT.
- Oxidation occurred both in vitro and in vivo.
- Oxidative modification altered HTT aggregate interactions and morphology.
Conclusions:
- Protein aggregates can be targets of oxidative modification.
- Post-aggregation oxidation regulates the properties of protein aggregates.
- This finding offers new insights into neurodegenerative disease mechanisms.
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