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Structural basis for recognition of the third SH3 domain of full‐length R85 (R85FL)/ponsin by ataxin‐7
Author(s) -
Jiang Ya-Jun,
Zhou Chen-Jie,
Zhou Zi-Ren,
Wu Meng,
Hu Hong-Yu
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.07.021
Subject(s) - microbiology and biotechnology , spinocerebellar ataxia , chemistry , nuclear protein , transcription factor , nuclear localization sequence , sh3 domain , activator (genetics) , biophysics , nucleus , biology , biochemistry , gene , signal transduction , proto oncogene tyrosine protein kinase src
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.