Home  |  Contact
PROSITE documentation PDOC51656 [for PROSITE entry PS51656]

4Fe-4S domain profile


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 Coβ-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 [1,2,3].

The 4Fe-4S domain lacks homology to the 4Fe-4S ferredoxin-type iron-sulfur binding domain (see <PDOC00176>), but is also found in bacterial electron transport complex protein RnfB [2].

The 4Fe-4S domain consists of four helices (three α-helices from H1-H3 and one 3(10)-helix with the order αH1-αH2-3(10)H-αH3) (see <PDB:2YCL>). 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 αH1 and αH2, connecting 3(10)H and αH3, and at the end of αH2. The [4Fe-4S] cluster is placed near the surface of the 4Fe-4S domain, but is shielded from the solvent by hydrophobic amino acids [2,3].

The profile we developed covers the entire 4Fe-4S domain.

Last update:

August 2012 / New entry.

Technical section

PROSITE method (with tools and information) covered by this documentation:

4FE4S, PS51656; 4Fe-4S domain profile  (MATRIX)


1AuthorsSvetlitchnaia T. Svetlitchnyi V. Meyer O. Dobbek H.
TitleStructural insights into methyltransfer reactions of a corrinoid iron-sulfur protein involved in acetyl-CoA synthesis.
SourceProc. Natl. Acad. Sci. U.S.A. 103:14331-14336(2006).
PubMed ID16983091

2AuthorsGoetzl S. Jeoung J.-H. Hennig S.E. Dobbek H.
TitleStructural basis for electron and methyl-group transfer in a methyltransferase system operating in the reductive acetyl-CoA pathway.
SourceJ. Mol. Biol. 411:96-109(2011).
PubMed ID21640123

3AuthorsKung Y. Ando N. Doukov T.I. Blasiak L.C. Bender G. Seravalli J. Ragsdale S.W. Drennan C.L.
TitleVisualizing molecular juggling within a B12-dependent methyltransferase complex.
SourceNature 484:265-269(2012).
PubMed ID22419154

PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)