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N-terminal tyrosine of ISCU2 triggers [2Fe-2S] cluster synthesis by ISCU2 dimerization
Sven-A Freibert1,2, Michal T Boniecki3, Claudia Stümpfig1
1Institut für Zytobiologie im Zentrum SYNMIKRO, Philipps-Universität Marburg, Karl-von-Frisch-Str. 14, 35032, Marburg, Germany.
Nature Communications
|November 26, 2021
Summary
The human mitochondrial ISCU2 protein requires Tyr35 for iron-sulfur (Fe/S) cluster synthesis. Ionic interactions between mutant ISCU2 proteins lacking Tyr35 can restore Fe/S cluster formation, highlighting Tyr35
Area of Science:
- Biochemistry
- Cell Biology
- Structural Biology
Background:
- Iron-sulfur (Fe/S) clusters are essential for numerous cellular processes.
- Scaffold proteins, like human mitochondrial ISCU2, are crucial for Fe/S cluster synthesis and transfer.
- The mechanism of [2Fe-2S] cluster formation and ISCU2 dimerization remains unclear.
Purpose of the Study:
- To elucidate the mechanism of [2Fe-2S] cluster formation and ISCU2 dimerization.
- To identify the role of the N-terminal Tyr35 residue in ISCU2 function.
Main Methods:
- Structural analysis
- Biochemical assays
- Cell biological experiments
Main Results:
- The N-terminal Tyr35 of ISCU2 is essential for late-stage [2Fe-2S] cluster formation and ISCU2 dimerization.
- Mixing two non-functional ISCU2 mutants (Asp35 and Lys35) restored wild-type ISCU2 maturation.
- Ionic interactions between mutant proteins can substitute for native Tyr-Tyr interactions in dimerization-induced cluster formation.
Conclusions:
- Tyr35 plays a critical mechanistic role in de novo mitochondrial [2Fe-2S] cluster synthesis.
- Ionic forces are sufficient to drive ISCU2 dimerization and cluster formation in the absence of Tyr35.
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