A pathway for assembling [4Fe-4S]2+ clusters in mitochondrial iron-sulfur protein biogenesis
| Autor: | Lucia Banci, Dafne Suraci, Veronica Nasta, Spyridon Gourdoupis, Simone Ciofi-Baffoni |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
biology Stereochemistry Cell Biology Mitochondrion Biochemistry BOLA3 GLRX5 iron–sulfur protein mitochondrial iron–sulfur cluster assembly machinery NFU1 Metallochaperones 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Monomer chemistry Biosynthesis Iron-sulfur protein GLRX5 030220 oncology & carcinogenesis Cluster (physics) biology.protein Molecular Biology Biogenesis |
| Popis: | During its late steps, the mitochondrial iron-sulfur cluster (ISC) assembly machinery leads to the formation of [4Fe-4S] clusters. In vivo studies revealed that several proteins are implicated in the biosynthesis and trafficking of [4Fe-4S] clusters in mitochondria. However, they do not provide a clear picture into how these proteins cooperate. Here, we showed that three late-acting components of the mitochondrial ISC assembly machinery (GLRX5, BOLA3, and NFU1) are part of a ISC assembly pathway leading to the synthesis of a [4Fe-4S]2+ cluster on NFU1. We showed that the [2Fe-2S]2+ GLRX5-BOLA3 complex transfers its cluster to monomeric apo NFU1 to form, in the presence of a reductant, a [4Fe-4S]2+ cluster bound to dimeric NFU1. The cluster formation on NFU1 does not occur with [2Fe-2S]2+ GLRX5, and thus, the [4Fe-4S] cluster assembly pathway is activated only in the presence of BOLA3. These results define NFU1 as an 'assembler' of [4Fe-4S] clusters, that is, a protein able of converting two [2Fe-2S]2+ clusters into a [4Fe-4S]2+ cluster. Finally, we found that the [4Fe-4S]2+ cluster bound to NFU1 has a coordination site which is easily accessible to sulfur-containing ligands, as is typically observed in metallochaperones. This finding supports a role for NFU1 in promoting rapid and controlled cluster-exchange reaction. |
| Databáze: | OpenAIRE |
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