title: Structural basis for recognition of the third SH3 domain of full-length R85 (R85FL)/ponsin by ataxin-7.
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.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Jiang
authors.forename: Chen-Jie
authors.initials: CJ
authors.lastname: Zhou
authors.forename: Zi-Ren
authors.initials: ZR
authors.lastname: Zhou
authors.forename: Meng
authors.initials: M
authors.lastname: Wu
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Hu
mesh_terms: D017398:Alternative Splicing; D000067719:Ataxin-7; D001665:Binding Sites; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry; D008840:Microfilament Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D055672:Static Electricity
chemical_list: C000593829:ATXN7 protein, human; D000067719:Ataxin-7; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; C119201:ponsin; C097188:polyglutamine
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