Elucidation of the splicing regulatory function of an intrinsically disordered protein PQBP1

• Project/Area Number: 15K07886
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: University of Toyama
• Principal Investigator: Mineyuki Mizuguchi 富山大学, 大学院医学薬学研究部(薬学), 教授 (30332662)
• Co-Investigator(Kenkyū-buntansha): 帯田 孝之 富山大学, 大学院医学薬学研究部(薬学), 准教授 (30578696)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: タンパク質 / 天然変性タンパク質 / 相互作用 / アロステリック効果 / SPR / 天然変性蛋白質 / NMR / アロステリック機構

Outline of Final Research Achievements

PQBP1 is composed of a small folded WW domain and a large disordered region. PQBP1 binds to a splicing factor WBP11 and a spliceosomal protein U5-15kD. The hydrophobic area of U5-15kD interacts with the YxxPxxVL motif located in the C-terminal region of PQBP1. In this study, we have shown that the interaction between PQBP1 and U5-15kD is attenuated by the binding of the N-terminal WW domain of PQBP1 to WBP11. Our results also showed that the interaction between U5-15kD and U5-52K strengthen the interaction between U5-15kD and PQBP1.

Research Products

• [Journal Article] Allosteric modulation of the binding affinity between PQBP1 and the spliceosomal protein U5-15kD (2016)
  • Author(s): Mizuguchi, M., Obita, T., Kajiyama, A., Kozakai, Y., Nakai, T., Nabeshima, Y., Okazawa, H.
  • Journal Title: FEBS Letters Volume: 590 Issue: 14 Pages: 2221-31
  • DOI: 10.1002/1873-3468.12256
  • Peer Reviewed
• [Journal Article] Frameshift mutations in the PQBP1 gene prevent its interaction with the splicing factor U5-15kD. (2015)
  • Author(s): Mizuguchi M.
  • Journal Title: Seikagaku Volume: 87 Pages: 478-480
  • NAID: 40020571922
• [Presentation] Interaction of spliceosomal proteins PQBP1, U5-15kD, and WBP11. (2016)
  • Author(s): Mizuguchi M, Nabeshima Y, Obita T, Okazawa H.
  • Organizer: The XXVIIth International Conference on Magnetic Resonance in Biological Systems
  • Place of Presentation: Kyoto
  • Year and Date: 2016-08-15
  • Int'l Joint Research
• [Presentation] NMRを用いた凝集性タンパク質の解析 (2015)
  • Author(s): 水口峰之
  • Organizer: 平成27年度日本分光学会ＮＭＲ分光部会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-09-30
  • Invited