The structure of the AXH domain of spinocerebellar ataxin-1.
Spinocerebellar ataxia type 1 is a late-onset neurodegenerative disease caused by the expansion of a CAG triplet repeat in the SCA1 gene. This results in the lengthening of a polyglutamine tract in the gene product ataxin-1. This produces a toxic gain of function that results in specific neuronal death. A region in ataxin-1, the AXH domain, exhibits significant sequence similarity to the transcription factor HBP1. This region of the protein has been implicated in RNA binding and self-association. We have determined the crystal structure of the AXH domain of ataxin-1. The AXH domain is dimeric and contains an OB-fold, a structural motif found in many oligonucleotide-binding proteins, supporting its proposed role in RNA binding. By structure comparison with other proteins that contain an OB-fold, a putative RNA-binding site has been identified. We also identified a cluster of charged surface residues that are well conserved among AXH domains. These residues may constitute a second ligand-binding surface, suggesting that all AXH domains interact with a common yet unidentified partner.
Chen
Yu Wai
YW
Centre for Protein Engineering, Medical Research Council Centre, Cambridge, UK.
Allen
Mark D
MD
Veprintsev
Dmitry B
DB
Löwe
Jan
J
Bycroft
Mark
M
D000595:Amino Acid Sequence; D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D018360:Crystallography, X-Ray; D019281:Dimerization; D004331:Drosophila melanogaster; D004926:Escherichia coli / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D009687:Nuclear Proteins / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry; D012097:Repressor Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014461:Ultracentrifugation
C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C486328:HBP1 protein, human; D006609:High Mobility Group Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D012097:Repressor Proteins; C097188:polyglutamine; D012313:RNA