Structural basis for recognition of the third SH3 domain of full-length R85 (R85FL)/ponsin by ataxin-7

Ya Jun Jiang, Chen Jie Zhou, Zi Ren Zhou, Meng Wu, Hong Yu Hu

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2905-2911
Number of pages7
JournalFEBS Letters
Issue number18
StatePublished - Sep 17 2013

Bibliographical note

Funding Information:
The authors would thank Dr. A. Brice for providing the plasmid coding for ataxin-7, Dr. C.W. Jin at Peking University for technical assistance in NMR data acquisition, and Dr. Alexander M.J.J. Bonvin for the help of generating the complex structure using HADDOCK software. This work was supported by the grants from the National Basic Research Program of China ( 2011CB911104, 2012CB911003 ), and the National Natural Science Foundation of China ( 10979070 ).


  • Ataxin-7
  • Inclusion body
  • Polyglutamine
  • Proline-rich region
  • R85FL/ponsin
  • SH3 domain


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