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Glutaredoxins with iron-sulphur clusters in eukaryotes - Structure, function and impact on disease
Carsten Berndt1, Loïck Christ2, Nicolas Rouhier2
1Department of Neurology, Medical Faculty, Heinrich-Heine University, Merowingerplatz1a, 40225 Düsseldorf, Germany.
Numerous glutaredoxins, proteins found in most organisms, bind iron-sulfur (Fe/S) clusters. This review highlights prominent Fe/S glutaredoxins involved in cellular iron metabolism.
Area of Science:
- Biochemistry
- Molecular Biology
- Protein Science
Background:
- Glutaredoxins are part of the thioredoxin superfamily, present across most organisms.
- A significant recent finding is that many glutaredoxins bind iron-sulfur (Fe/S) clusters, impacting their function.
- Fe/S cluster binding is observed in Class I, II, and III glutaredoxins, including monothiol and dithiol subfamilies.
Purpose of the Study:
- To review recent advancements in the understanding of prominent eukaryotic Fe/S glutaredoxins.
- To summarize the functional properties and roles of these Fe/S binding proteins.
- To highlight specific examples like glutaredoxin 5, S14, S16, and 2.
Main Methods:
- Literature review of recent developments in Fe/S glutaredoxin research.
- Analysis of characterized glutaredoxin structures and functions.
- Comparative study of different glutaredoxin classes and their Fe/S cluster coordination.
Main Results:
- Fe/S clusters, typically [2Fe2S], are coordinated by active-site cysteines and glutathione in dimeric glutaredoxin complexes.
- Monothiol glutaredoxins, unlike dithiol types, exhibit limited oxidoreductase activity but are crucial for iron metabolism.
- Key Fe/S glutaredoxins discussed include mitochondrial Grx5, chloroplastic GrxS14/S16, and nuclear/cytosolic Grx3.
Conclusions:
- Fe/S cluster binding is a key functional feature for numerous glutaredoxins across different classes.
- Monothiol glutaredoxins play a vital role in cellular iron homeostasis.
- This review consolidates current knowledge on prominent eukaryotic Fe/S glutaredoxins, emphasizing their diverse roles.
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