4Fe-4S cluster assembles on CFD1:NBP35 scaffold

Stable Identifier
R-SCE-2564822
Type
Reaction [omitted]
Species
Saccharomyces cerevisiae
Compartment
General
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4Fe-4S cluster assembles on CFD1:NBP35 scaffold

A [4Fe-4S] cluster is assembled on a scaffold composed of the P-loop NTPases Cfd1 (human NUBP2) and Nbp35 (human NUBP1) in a nucleotide-dependent fashion. The two proteins form a heterotetramer which transiently binds the [4Fe-4S] cluster in a bridged form between two subunits of the complex. The Fe/S cluster is bound to two highly conserved Cys residues in the C-termini of each of these proteins. Nbp35 contains an additional, stably associated [4Fe-4S] cluster at its N-terminus which is essential for function.
Mitochondria play a crucial role in cytosolic and nuclear Fe/S protein biogenesis. They export via a mitochondrial ABC transporter (yeast ATM1, human ABCB7) a still unknown, sulfur-containing compound which is essential for Fe/S cluster assembly in the cytosol.
The general cytosolic iron donor, the multi-domain monothiol glutaredoxin (yeast Grx3-Grx4, human GRX3 or PICOT) plays a crucial role in cytosolic-nuclear Fe/S protein biogenesis. The precise molecular function of the glutaredoxin is still unclear.

Literature References
PubMed ID Title Journal Year
19385603 Crucial role of conserved cysteine residues in the assembly of two iron-sulfur clusters on the CIA protein Nar1

Pierik, AJ, Lill, R, Urzica, E, Mühlenhoff, U

Biochemistry 2009
22362766 A bridging [4Fe-4S] cluster and nucleotide binding are essential for function of the Cfd1-Nbp35 complex as a scaffold in iron-sulfur protein maturation

Bill, E, Netz, DJ, Pallesen, LJ, Pierik, AJ, Lill, R, Walden, WE, Stümpfig, M, Sharma, AK

J. Biol. Chem. 2012
17401378 The Cfd1-Nbp35 complex acts as a scaffold for iron-sulfur protein assembly in the yeast cytosol

Netz, DJ, Pierik, AJ, Lill, R, Stümpfig, M, Mühlenhoff, U

Nat. Chem. Biol. 2007
15728363 The eukaryotic P loop NTPase Nbp35: an essential component of the cytosolic and nuclear iron-sulfur protein assembly machinery

Pierik, AJ, Lill, R, Balk, J, Aguilar Netz, DJ, Hausmann, A, Mühlenhoff, U

Proc. Natl. Acad. Sci. U.S.A. 2005
12970194 A novel eukaryotic factor for cytosolic Fe-S cluster assembly

Roy, A, Nicholson, T, Walden, WE, Solodovnikova, N, Antholine, W

EMBO J. 2003
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Catalyst Activity

electron transfer activity of TAH18:DRE2 reduced [cytosol]

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