4Fe-4S domain (IPR007202)

Short name: 4Fe-4S_dom

Overlapping homologous superfamilies


Domain relationships



The cobalt- and iron-containing corrinoid iron-sulfur protein (CoFeSP) is functional in the acetyl-CoA pathway of autotrophic carbon fixation in various bacteria and acrchaea, where it is essential for the biosynthesis of acetyl- CoA. CoFeSP acts in two methylation reactions: the transfer of a methyl group from methyltransferase (MeTr)-bound methyltetrahydrofolate to the cob(I)amide of CoFeSP and the transfer of the methyl group of methyl-cob(III)amide to the reduced Ni-Ni-[4Fe-4S] active site cluster A of acetyl-CoA synthase (ACS). CoFeSP is a heterodimer consisting of a large subunit (CfsA) and a small subunit (CfsB). The large subunit has three domains: an amino (N)-terminal 4Fe-4S domain, a TIM barrel domain and a carboxy (C)-terminal domain that binds CoBeta-aqua-(5,6-dimethylbenzimiddazolylcobamide) (corrinoid). Methylation of CoFeSP only occurs in the low potential Co(I) state, which can be sporadically oxidized to the inactive Co(II) state, making its reductive reactivation necessary. The low-potential [4Fe-4S]2(+)/1(+) cluster is involved in the reductive reactivation of CoFeSP and is able to transfer electrons to cob(II)amide from NiFe-containing carbon monoxyde dehydrogenase (CODH), pyruvate:ferredoxin oxydoreductase or reduced ferredoxins [PMID: 16983091, PMID: 21640123, PMID: 22419154].

The 4Fe-4S domain lacks homology to the 4Fe-4S ferredoxin-type iron-sulfur binding domain, but is also found in bacterial electron transport complex protein RnfB [PMID: 21640123].

The 4Fe-4S domain consists of four helices (three alpha-helices from H1-H3 and one 3(10)-helix with the order alphaH1-alphaH2-3(10)H-alphaH3). This four-helix-bundle-like architecture positions the four cysteinyl ligands of the [4Fe-4S] cluster. The iron-sulfur cluster binding motif Cys-X(2)-Cys-X(4)-Cys-X(16)-Cys is located at loops connecting alphaH1 and alphaH2, connecting 3(10)H and alphaH3, and at the end of alphaH2. The [4Fe-4S] cluster is placed near the surface of the 4Fe-4S domain, but is shielded from the solvent by hydrophobic amino acids [PMID: 21640123, PMID: 22419154].

This entry represents the 4Fe-4S domain.

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0051536 iron-sulfur cluster binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles