RdCVFs: Bifunctional Thioredoxin–Like Proteins Yielding to Cone Viability

Abstract

Abstract: : Purpose: The mouse model for retinitis Pigmentosa rd1 allowed identification of a rod–derived cone viability factor, RdCVF/Txnl–6. With this present study we want to gain insight into aspects for the genomic organization of the corresponding locus, eventual transcriptional variants and resulting molecular properties for the resulting gene product. Methods: RdCVF has been identified by expression cloning using a functional assay based on cone viability. Novel bioinformatics protocols (RetScope) evaluating high quality sequence alignments (MACS) between species on genome level were used in combination with motif recognition and structure prediction and homology modelling Results: We have identified RdCVF/Txnl–6 as novel evolutionary conserved eukaryotic protein with a thioredoxin–like fold defining as new class of bifunctional proteins with a short extracellular form specifically expressed by photoreceptors and involved in cone viability, and one long form having potentially a thiol–oxidoreductase activity. In the context of an evolutionary study in all the complete genomes available, we have identified RdCVF orthologous proteins in all vertebrate species whose genome sequence is available. In addition to strong sequence conservation, these proteins have preserved specific characteristic that could be traced form Nematodes to Mammals, including common genic organization, splicing variant forms, tissue specificity expression and structural features close to the tryparedoxin fold. Conclusions: These data strongly emphasize that RdCVF may represent one of the most promising stakes in the therapeutic approach for an inherited retinal disease leading to blindness.

Keywords: protein structure/function • candidate gene analysis • cell death/apoptosis