CDR Proteins of C. elegans and Related Species: Relationship to Metaxin and FAXC Proteins

CDR (cadmium-responsive) proteins of the nematode C. elegans and related species are shown to have structural homology to metaxin proteins and FAXC (failed axon connections) proteins of vertebrates and invertebrates. Unlike the metaxin and FAXC proteins, however, the predicted CDR proteins are only encoded in the genomes of nematodes, and not in vertebrates or other invertebrates. Metaxin-like structural features of CDR proteins are shown in this report to include: (1) GST_N_Metaxin and GST_C_Metaxin conserved protein domains, (2) metaxin-like patterns of -helical secondary structure, and (3) a special 4-stranded {beta}-sheet motif shared with the metaxins. FAXC proteins also possess these structural features. Phylogenetic analysis revealed that CDR proteins are related to metaxins 1, 2, and 3 and to FAXC proteins, although more closely to FAXC proteins. Nevertheless, all three types of proteins - CDR, FAXC, and metaxin - are related by evolution. Although CDR proteins have structural homology to metaxin and FAXC proteins, pairwise alignments of CDR proteins with metaxins and FAXCs demonstrated only low percentages of identical amino acids. CDR proteins can therefore be considered a separate category of proteins, distinct from metaxin and FAXC proteins. The CDR genes of C. elegans consist of a family of seven genes, cdr-1 to cdr-7, which form a cluster of closely adjacent genes on chromosome V. Multiple genes were also found for the related species C. briggsae and C. remanei. Alignment of pairs of C. elegans CDR protein sequences encoded by different cdr genes demonstrated a high level of sequence homology. The neighboring genes of the C. elegans cdr genes are different than the genes adjacent to the C. elegans faxc genes and the mtx-1 and mtx-2 metaxin genes.