Ataxin-7 (Atx7) is a component of the nuclear transcription co-activator complex; its polyglutamine (polyQ) expansion may cause nuclear accumulation and recruit numerous proteins to the intranuclear inclusion bodies. Full-length R85 (R85FL) is such a protein sequestered by polyQ-expanded Atx7. Here, we report that Atx7 specifically interacts with the third SH3 domain (SH3C) of R85FL through its second portion of proline-rich region (PRR). NMR structural analysis of the SH3C domain and its complex with PRR revealed that SH3C contains a large negatively charged surface for binding with the RRTR motif of Atx7. Microscopy imaging demonstrated that sequestration of R85FL by the polyQ-expanded Atx7 in cell is mediated by this specific SH3C-PRR interaction, which is implicated in the pathogenesis of spinocerebellar ataxia 7.
Keywords: Ataxin-7; Atx7; Inclusion body; PRR; Polyglutamine; Proline-rich region; R85FL; R85FL/ponsin; SCA7; SH3; SH3 domain; Src homology 3; ataxin-7; full-length R85; polyQ; polyglutamine; proline-rich region; spinocerebellar ataxia 7.
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