CDR Proteins ofC.elegansand Related Species: Relationship to Metaxin and FAXC Proteins

Abstract

ABSTRACTCDR (cadmium-responsive) proteins of the nematodeC. elegansand 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 α-helical secondary structure, and (3) a special 4-stranded β-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 ofC. elegansconsist of a family of seven genes,cdr-1tocdr-7, which form a cluster of closely adjacent genes on chromosome V. Multiple genes were also found for the related speciesC. briggsaeandC. remanei. Alignment of pairs ofC. elegansCDR protein sequences encoded by differentcdrgenes demonstrated a high level of sequence homology. The neighboring genes of theC.elegans cdrgenes are different than the genes adjacent to theC.elegans faxcgenes and themtx-1andmtx-2metaxin genes.