Conserved phosphoprotein interaction motif is functionally interchangeablebetween ataxin-7 and arrestins

Olivopontocerebellar atrophy with retinal degeneration is a hereditary neur odegenerative disorder that belongs to the subtype II of the autosomal domi nant cerebellar ataxias and is characterized by early-onset cerebellar and macular degeneration preceded by diagnostically useful tritan colorblindnes s. The gene mutated in the disease (SCA7) has been mapped to chromosome 3p1 2 13.5, and positional cloning identified the cause of the disease as CAG r epeat expansion in this gene. The SCA 7 gene product, ataxin7, is an 897 am ino acid protein with an expandable polyglutamine tract close to its N-term inus. No clues to ataxin-7 function have been obtained from sequence databa se searches. Here we report that ataxin-7 has a motif of ca, 50 amino acids , related to the phosphate-binding site of arrestins, To test the relevance of this sequence similarity, we introduced the putative ataxin-7 phosphate -binding site into visual arrestin and beta-arrestin. Both chimeric arresti ns retain receptor-binding affinity and show characteristic high selectivit y for phosphorylated activated forms of rhodopsin and beta-adrenergic recep tor, respectively. Although the insertion of a Gly residue (absent in arres tins but present in the putative phosphate-binding site of ataxin-7) disrup ts the function of visual arrestin-ataxin-7 chimera, it enhances the functi on of beta-arrestin-ataxin-7 chimera. Taken together, our data suggest that the arrestin-like site in the ataxin-7 sequence is a functional phosphate- binding site. The presence of the phosphate-binding site in ataxin-7 sugges ts that this protein may be involved in phosphorylation-dependent binding t o its protein partner(s) in the cell.