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

Stable Identifier
R-SCE-2564822
Type
Reaction [omitted]
Species
Saccharomyces cerevisiae
Compartment
General
SVG |   | PPTX  | SBGN
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
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
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
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
12970194 A novel eukaryotic factor for cytosolic Fe-S cluster assembly

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

EMBO J. 2003
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
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Catalyst Activity

electron transfer activity of TAH18:DRE2 reduced [cytosol]

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