Structure and function of moyamoya disease-associated protein, mysterin

• Project/Area Number: 25840024
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: Kyoto Sangyo University
• Principal Investigator: MORITO Daisuke 京都産業大学, 総合生命科学部, 研究員 (20514251)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ミステリン / モヤモヤ病 / AAA+タンパク質 / ユビキチン / mysterin / RNF213 / AAA+ ATPアーゼ

Outline of Final Research Achievements

We demonstrated that mysterin contains enzymatically active AAA+ ATPase modules, forms large troidal oligomer through these modules, and dynamically changes its structural state. Furthermore, we demonstrated that mysterin is indispensble for neuro, muscular, and vascular development in vivo using zebrafish model. The two enzymatic activities of mysterin are both essential for this function.

Research Products

• [Journal Article] Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ AT Pase, which dynamically changes its oligomeric state (2014)
  • Author(s): Daisuke Morito, Kouki Nishikawa, Jun Houseki, Akira Kitamura, Yuri Kotani, Kazumi Kiso, Masataka Kinjo, Yoshimori Fujiyoshi & Kazuhiro Nagata
  • Journal Title: SCIENTIFIC REPORTS Volume: Vol. 4 Issue: 1 Pages: 4442-4442
  • DOI: 10.1038/srep04442
  • Peer Reviewed / Open Access
• [Journal Article] The moyamoya disease susceptibility variant RNF213 R4810K (rs112735431) (2013)
  • Author(s): Hitomi T, Habu T, Kobayashi H, Okuda H, Harada KH, Osafune K, Taura D, Sone M, Asaka I, Ameku T, Watanabe A, Kasahara T, Sudo T, Shiota F, Hashikata H, Takagi Y, Morito D, Miyamoto S, Nakao K, Koizumi A
  • Journal Title: Biochem Biophys Res Commun. Volume: 439(4) Issue: 4 Pages: 419-426
  • DOI: 10.1016/j.bbrc.2013.08.067
  • Peer Reviewed
• [Journal Article] Downregulation of Securin by the variant RNF213 R4810K (rs112735431, G>A) reduces angiogenic activity of induced pluripotent stem cell-derived vascular endothelial cells from moyamoya patients. (2013)
  • Author(s): Hitomi T, Habu T, Kobayashi H, Okuda H, Harada KH, Osafune K, Taura D, Sone M, Asaka I, Ameku T, Watanabe A, Kasahara T, Sudo T, Shiota F, Hashikata H, Takagi Y, Morito D, Miyamoto S, Nakao K, Koizumi A.
  • Journal Title: Biochem Biophys Res Commun. Volume: 438(1): Issue: 1 Pages: 13-19
  • DOI: 10.1016/j.bbrc.2013.07.004
  • Peer Reviewed
• [Presentation] モヤモヤ病の鍵因子 巨大ATPアーゼ／ユビキチンリガーゼ・ミステリンの構造と機能 (2015)
  • Author(s): 森戸大介
  • Organizer: 京都大学大学院理学研究科 動物学セミナー
  • Place of Presentation: 京都大学理学部
  • Year and Date: 2015-01-13
  • Invited
• [Presentation] モヤモヤ病タンパク質ミステリンの構造と機能 (2014)
  • Author(s): 森戸大介
  • Organizer: 第36回日本生物学的精神医学会・第57回日本神経化学会大会 合同年会
  • Place of Presentation: 奈良県立新公会堂
  • Year and Date: 2014-09-30
  • Invited
• [Presentation] Structure and function of moyamoya disease-associated AAA+ ATPase/ubiquitin ligase mysterin (2013)
  • Author(s): Morito D, Kotani Y, Nishikawa K, Hoseki J, Yamazaki S, Iemura S, Natsume T, Takashima S, Fujiyoshi Y, Nagata K
  • Organizer: The 35th Naito Conference: The Ubiquitin-Proteasome System
  • Place of Presentation: Chateux Gateaux Kingdom Sapporo, Sapporo, Japan
• [Presentation] Protential dynamic equilibrium of moyamoya disease-associated AAA+ ATPase mysterin. (2013)
  • Author(s): Morito D, Nishikawa K, Hoseki J, Kitamura A, Kotani Y, Kinjo M, Fujiyoshi Y, Nagata K
  • Organizer: EMBO workshop”AAA+ proteins:from mechanism and disease to targets”
  • Place of Presentation: Commundo Tagungshotel, Neuss, Germany