InterPro domain: IPR018967

This entry represents iron-sulphur domain containing proteins that have a CDGSH sequence motif (although the Ser residue can also be an Ala or Thr), and is found in proteins from a wide range of organisms with the exception of fungi. The CDGSH-type domain binds a redox-active pH-labile 2Fe-2S cluster. The conserved sequence C-X-C-X2-(S/T)-X3-P-X-C-D-G-(S/A/T)-H is a defining feature of this family [ 1 ].

CDGSH-type domains are found in mitoNEET, an iron-containing integral protein of the outer mitochondrian membrane (OMM). MitoNEET forms a dimeric structure with a NEET fold, and contains two domains: a beta-cap region and a cluster-binding domain that coordinated two acid-labile 2Fe-2S clusters (one bound to each protomer) [ 2 ]. The CDGSH iron-sulphur domain is oriented towards the cytoplasm and is tethered to the mitochondrial membrane by a more N-terminal domain found in higher vertebrates, ( IPR019610 ) [ 3 , 4 ]. The whole protein regulates oxidative capacity and may function in electron transfer, for instance in redox reactions with metabolic intermediates, cofactors and/or proteins localized at the OMM.

1. MitoNEET is an iron-containing outer mitochondrial membrane protein that regulates oxidative capacity. Proc. Natl. Acad. Sci. U.S.A. 104, 5318-23
2. MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone. Proc. Natl. Acad. Sci. U.S.A. 104, 14342-7
3. The outer mitochondrial membrane protein mitoNEET contains a novel redox-active 2Fe-2S cluster. J. Biol. Chem. 282, 23745-9