title: Conserved phosphoprotein interaction motif is functionally interchangeable between ataxin-7 and arrestins.
abstract: Olivopontocerebellar atrophy with retinal degeneration is a hereditary neurodegenerative disorder that belongs to the subtype II of the autosomal dominant cerebellar ataxias and is characterized by early-onset cerebellar and macular degeneration preceded by diagnostically useful tritan colorblindness. The gene mutated in the disease (SCA7) has been mapped to chromosome 3p12-13.5, and positional cloning identified the cause of the disease as CAG repeat expansion in this gene. The SCA7 gene product, ataxin-7, is an 897 amino acid protein with an expandable polyglutamine tract close to its N-terminus. No clues to ataxin-7 function have been obtained from sequence database 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 arrestins retain receptor-binding affinity and show characteristic high selectivity for phosphorylated activated forms of rhodopsin and beta-adrenergic receptor, respectively. Although the insertion of a Gly residue (absent in arrestins but present in the putative phosphate-binding site of ataxin-7) disrupts the function of visual arrestin-ataxin-7 chimera, it enhances the function 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 suggests that this protein may be involved in phosphorylation-dependent binding to its protein partner(s) in the cell.
authors.affiliation: Ralph and Muriel Roberts Laboratory for Vision Science, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, Arizona 85351, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Mushegian
authors.forename: S A
authors.initials: SA
authors.lastname: Vishnivetskiy
authors.forename: V V
authors.initials: VV
authors.lastname: Gurevich
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019390:Arrestins / Q000737:chemistry* / Q000235:genetics; D000067719:Ataxin-7; D001665:Binding Sites; D002417:Cattle; D017124:Conserved Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics; D010710:Phosphates / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins; D013132:Spinocerebellar Degenerations / Q000235:genetics
chemical_list: C000593829:ATXN7 protein, human; D019390:Arrestins; D000067719:Ataxin-7; D009419:Nerve Tissue Proteins; D010710:Phosphates; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins