Mitochondrial Carrier Family (MCF)
The mitochondrial carrier family (MCF)
MCF proteins are located mainly in the inner mitochondrial membrane and mediate the transport of a broad variety of metabolites and cofactors. They consist of three tandem repeats of a domain of approximately 100 residues, each domain containing two transmembrane (TM) helices (Fig1). MCF proteins are easily recognized by three repeats of a bipartite signature. The first part, Px[DE]xh[KR]x[KR] (where h is usually hydrophobic), is separated from the second part of the signature, [DE]Gxxxx[FYW][KR]G, by 20 to 30 residues. At the structural level, the proline residues of the first motif of the profile induce kinks in the odd-numbered TM helices H1, H3, and H5 whereas the second motif is located in the short helices h1-2, h3-4, and h5-6 facing the mitochondrial matrix.
The mitochondrial ADP/ATP carrier
On the basis of the typical MCF signature indicated above, it was found that the genome of Dictyostelium discoideum harbors 31 genes encoding different MCF proteins (Satre et al., 2007). Further phylogenetic analysis (see Fig2), sequence comparison to MCF proteins characterized in other organisms and identification of the amino acids involved in the substrate selectivity filter (Kunji and Robinson, 2006; Nury et al., 2006) show that Dictyostelium MCF members belong to different substrate classes including 13 nucleotide carriers, 10 amino acid carriers, 3 uncoupler proteins, 3 keto acid carriers, 1 Pi carrier and 1 iron carrier (mitoferrin) as detailed below.
- Nucleotide carrier class: [McfA], [McfB], [McfC], [McfV] (ATP-Mg2+/Pi), [McfP], [McfR] (Coenzyme A); [McfI], [McfM] (folate); [AncA] (ADP/ATP); [McfK] (deoxynucleotide), [McfQ] (ATP - peroxisomal type); [McfW] (NAD+); and [RimA] (pyrimidine nucleotide).
- Amino acid carrier class: [McfD], [McfG], [McfL], [McfS], [McfY] (carnitine or ornithine); [McfE], [McfO], [McfU], [McfX] (aspartate/glutamate).
- Keto acid class: [McfJ], [McfT] (2-oxodicarboxylate); [McfZ] (dicarboxylate/tricarboxylate).
- Uncoupler protein type: [UcpA], [UcpB], [UcpC] (H+ - fatty acids)
- Pi carrier: [McfN]
- Iron carrier: [McfF] (mitoferrin)
- Bof, M., Brandolin, G., Satre, M. and Klein, G. (1999). The mitochondrial adenine nucleotide translocator from Dictyostelium discoideum. Functional characterization and DNA sequencing. Eur. J. Biochem. 259, 795-800.
- Kunji, E. R. and Robinson, A. J. (2006). The conserved substrate binding site of mitochondrial carriers. Biochim. Biophys. Acta 1757, 1237-1248.
- Nury, H., Dahout-Gonzalez, C., Trezeguet, V., Lauquin, G. J., Brandolin, G. and Pebay-Peyroula, E. (2006). Relations between structure and function of the mitochondrial ADP/ATP carrier. Annu. Rev. Biochem. 75, 713-741.
- Satre, M., Mattei, S., Aubry, L., Gaudet, P., Pelosi, L., Brandolin, G. and Klein, G. (2007). Mitochondrial carrier family. Repertoire and peculiarities of the cellular slime mould Dictyostelium discoideum. Biochimie, in press (doi: 10.1016/j.biochi.2007.1003.1004).
Provided by Gerard Klein and Michel Satre, April 2007