Abstract
Cytosolic and nuclear iron-sulfur (Fe-S) proteins are involved in many essential pathways including translation and DNA maintenance. Their maturation requires the cytosolic Fe-S protein assembly (CIA) machinery. To identify new CIA proteins we employed systematic protein interaction approaches and discovered the essential proteins Yae1 and Lto1 as binding partners of the CIA targeting complex. Depletion of Yae1 or Lto1 results in defective Fe-S maturation of the ribosome-associated ABC protein Rli1, but surprisingly no other tested targets. Yae1 and Lto1 facilitate Fe-S cluster assembly on Rli1 in a chain of binding events. Lto1 uses its conserved C-terminal tryptophan for binding the CIA targeting complex, the deca-GX3 motifs in both Yae1 and Lto1 facilitate their complex formation, and Yae1 recruits Rli1. Human YAE1D1 and the cancer-related ORAOV1 can replace their yeast counterparts demonstrating evolutionary conservation. Collectively, the Yae1-Lto1 complex functions as a target-specific adaptor that recruits apo-Rli1 to the generic CIA machinery.
Highlights
Maturation of iron-sulfur (Fe-S) proteins in eukaryotes depends on the coordinated action of complex proteinaceous machineries in mitochondria and cytosol (Lill, 2009; Stehling and Lill, 2013; Lukes and Basu, 2015; Maio and Rouault, 2015)
Maturation of cytosolic and nuclear Fe-S proteins is further assisted by the cytosolic Fe-S protein assembly (CIA) machinery that is conserved in virtually all eukaryotes (Sharma et al, 2010; Netz et al, 2014; Paul and Lill, 2015)
In this work we have identified and functionally characterized the essential proteins Yae1 and Lto1 as two novel members of the CIA machinery
Summary
Maturation of iron-sulfur (Fe-S) proteins in (non-plant) eukaryotes depends on the coordinated action of complex proteinaceous machineries in mitochondria and cytosol (Lill, 2009; Stehling and Lill, 2013; Lukes and Basu, 2015; Maio and Rouault, 2015). The mitochondrial iron-sulfur cluster (ISC) assembly machinery generates the organellar Fe-S proteins but is essential for the biogenesis of cytosolic and nuclear Fe-S proteins (Kispal et al, 1999; Gerber et al, 2004; Biederbick et al, 2006). Maturation of cytosolic and nuclear Fe-S proteins is further assisted by the cytosolic Fe-S protein assembly (CIA) machinery that is conserved in virtually all eukaryotes (Sharma et al, 2010; Netz et al, 2014; Paul and Lill, 2015). The first known step of this biosynthetic process involves the de novo assembly of a [4Fe-4S] cluster on the scaffold protein complex consisting of the two related P-loop NTPases Cfd and Nbp
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