1. Structural basis for recognition of the third SH3 domain of full-length R85 (R85FL)/ponsin by ataxin-7
- Author
-
Zi-Ren Zhou, Chen Jie Zhou, Meng Wu, Hong-Yu Hu, and Ya Jun Jiang
- Subjects
Models, Molecular ,Ataxin 7 ,Recombinant Fusion Proteins ,Molecular Sequence Data ,Static Electricity ,Biophysics ,Gene Expression ,Intranuclear Inclusion Body ,Nerve Tissue Proteins ,Biology ,Proline-Rich Region ,Biochemistry ,SH3 domain ,Nuclear accumulation ,Structural Biology ,Transcription (biology) ,R85FL/ponsin ,Genetics ,medicine ,Escherichia coli ,Humans ,Protein Interaction Domains and Motifs ,Molecular Biology ,Inclusion body ,Ataxin-7 ,Cell Nucleus ,Inclusion Bodies ,Binding Sites ,Microfilament Proteins ,A protein ,Cell Biology ,medicine.disease ,Cell biology ,Alternative Splicing ,HEK293 Cells ,Spinocerebellar ataxia ,biology.protein ,Proline-rich region ,Peptides ,Polyglutamine ,Sequence Alignment ,Protein Binding - Abstract
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.
- Published
- 2013