Structural and functional analyses of Mmm1 and Mdm12 in the ERMES complex

• Project/Area Number: 25840020
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: Kyoto Sangyo University (2014-2015); Nagoya University (2013)
• Principal Investigator: KAWANO Shin 京都産業大学, 総合生命科学部, 研究助教 (90431676)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 結晶構造 / オルガネラネットワーク / リン脂質 / タンパク質複合体 / リン脂質輸送 / ホモロジーモデル / 単離ミトコンドリア / 結晶構造解析 / リポソーム

Outline of Final Research Achievements

The ERMES complex was recently found to be involved in the tethering system between ER and mitochondria in yeast. The complex consists of four core components (Mmm1, Mmm2, Mdm10, and Mdm12) and is supposed as a transducer of phospholipids between those two organelle. In this study, we succeeded in determining the crystal structure of Mdm12. In addition, the functional analyses of Mdm12 and Mdm12-Mmm1 soluble domain complex were also performed.
The crystal structure of Mdm12 belongs to SMP domain fold, which can accommodate a phospholipid in its cave structure. Furthermore, in vitro lipid transfer assay using Mdm12 and Mdm12-Mmm1 complex showed that the lipid transfer activity of Mdm12 was largely enhanced by forming a hetero oligomeric complex with Mmm1. These observations indicate that ERMES complex transfers phospholipids between the ER and mitochondrial outer membrane via Mdm12-Mmm1 complex as a minimal unit.

Research Products

• [Journal Article] Structural and mechanistic insights into phospholipid transfer by Ups1–Mdm35 in mitochondria. (2015)
  • Author(s): Watanabe, Y., Tamura, Y., Kawano, S., and Endo T.
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 772-772
  • DOI: 10.1038/ncomms8922
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Mdm12とMmm1によるリン脂質輸送メカニズムの解明 (2015)
  • Author(s): 河野慎、遠藤斗志也
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県・神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 膜間リン脂質輸送の構造生物学 (2015)
  • Author(s): 河野慎、渡邊康紀、田村康、遠藤斗志也
  • Organizer: 第67回細胞生物学会大会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-06-30
  • Invited
• [Presentation] ERMES複合体によるリン脂質輸送の構造基盤 (2015)
  • Author(s): 河野慎、遠藤斗志也
  • Organizer: 第15回蛋白質科学会年会
  • Place of Presentation: あわぎんホール（徳島県徳島市）
  • Year and Date: 2015-06-24
• [Presentation] ERMES複合体構成因子Mdm12およびMmm1によるリン脂質輸送メカニズムの解明 (2014)
  • Author(s): 河野慎、浅井絵里、スチンバラ、遠藤斗志也
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都市左京区岩倉大鷺町422番地国立京都国際会館
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] 小胞体ーミトコンドリア繋留複合体（ERMES複合体）構成因子Mdm12の構造機能相関 (2014)
  • Author(s): 河野慎、浅井絵里、スチンバラ、遠藤斗志也
  • Organizer: 第14回日本蛋白質科学会年会
  • Place of Presentation: 神奈川県横浜市中区山下町24-1ワークピア横浜
  • Year and Date: 2014-06-25 – 2014-06-27
• [Presentation] ERMES複合体構成タンパク質Mdm12の構造解析 (2013)
  • Author(s): 河野慎，スチンバラ，遠藤斗志也
  • Organizer: 第13回日本蛋白質科学会年会
  • Place of Presentation: 鳥取
• [Presentation] ERMES複合体構成タンパク質Mdm12の構造解析 (2013)
  • Author(s): 河野慎，スチンバラ，遠藤斗志也
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] Structural analysis of Mdm12 (2013)
  • Author(s): Shin Kawano, Si-quinbala, Eri Asai, and Toshiya Endo
  • Organizer: DynaMito 2013: The 4th International Symposium on Dynamics of Mitochondria - from Molecular Mechanisms to Physiological Functions and Disease
  • Place of Presentation: 沖縄