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Mutations in the PQBP1 gene prevent its interaction with the spliceosomal protein U5–15kD

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  • Mineyuki Mizuguchi

    (Faculty of Pharmaceutical Sciences, University of Toyama
    2630, Sugitani
    Graduate School of Innovative Life Science, University of Toyama
    2630, Sugitani)

  • Takayuki Obita

    (Faculty of Pharmaceutical Sciences, University of Toyama
    2630, Sugitani)

  • Tomohito Serita

    (Faculty of Pharmaceutical Sciences, University of Toyama
    2630, Sugitani)

  • Rieko Kojima

    (Faculty of Pharmaceutical Sciences, University of Toyama
    2630, Sugitani
    Present address: Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan)

  • Yuko Nabeshima

    (Faculty of Pharmaceutical Sciences, University of Toyama
    2630, Sugitani
    Graduate School of Innovative Life Science, University of Toyama
    2630, Sugitani)

  • Hitoshi Okazawa

    (Medical Research Institute, Tokyo Medical and Dental University; 1-5-45, Yushima, Bunkyo-ku
    1-5-45, Yushima, Bunkyo-ku
    Center for Brain Integration Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku)

Abstract

A loss-of-function of polyglutamine tract-binding protein 1 (PQBP1) induced by frameshift mutations is believed to cause X-linked mental retardation. However, the mechanism by which structural changes in PQBP1 lead to mental retardation is unknown. Here we present the crystal structure of a C-terminal fragment of PQBP1 in complex with the spliceosomal protein U5–15kD. The U5–15kD hydrophobic groove recognizes a YxxPxxVL motif in PQBP1, and mutations within this motif cause a loss-of-function phenotype of PQBP1 in vitro. The YxxPxxVL motif is absent in all PQBP1 frameshift mutants seen in cases of mental retardation. These results suggest a mechanism by which the loss of the YxxPxxVL motif could lead to the functional defects seen in this type of mental retardation.

Suggested Citation

  • Mineyuki Mizuguchi & Takayuki Obita & Tomohito Serita & Rieko Kojima & Yuko Nabeshima & Hitoshi Okazawa, 2014. "Mutations in the PQBP1 gene prevent its interaction with the spliceosomal protein U5–15kD," Nature Communications, Nature, vol. 5(1), pages 1-8, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4822
    DOI: 10.1038/ncomms4822
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    Cited by:

    1. Meihua Jin & Hiroki Shiwaku & Hikari Tanaka & Takayuki Obita & Sakurako Ohuchi & Yuki Yoshioka & Xiaocen Jin & Kanoh Kondo & Kyota Fujita & Hidenori Homma & Kazuyuki Nakajima & Mineyuki Mizuguchi & Hi, 2021. "Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation," Nature Communications, Nature, vol. 12(1), pages 1-22, December.

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