Comprehensive study of structure and dynamics of laminopathy-causing LMNA mutants for elucidation of Laminopathy

• Project/Area Number: 26840050
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biophysics
• Research Institution: Osaka University
• Principal Investigator: SUGIKI Toshihiko 大阪大学, たんぱく質研究所, 助教 (70635698)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: NMR / 核ラミン

Outline of Final Research Achievements

In order to demonstrate how structural and physicochemical changes of Lamin A(LMNA) are induced by laminopathy-causing mutations, we investigated tertiary structures and dynamics of LMNA Ig-like domain by NMR by developing the “MagRO-FLYA-CYANA” system for fully-automated NMR assignment and structure determination. As a result, we determined the tertiary structures of 5 mutants of the LMNA Ig-like domain. These mutants cause different types of laminopathy.

Research Products

• [Journal Article] Amorphous Aggregation of Cytochrome c with Inherently Low Amyloidogenicity Is Characterized by the Metastability of Supersaturation and the Phase Diagram (2016)
  • Author(s): Lin Yuxi, Kardos József, Imai Mizue, Ikenoue Tatsuya, Kinoshita Misaki, Sugiki Toshihiko, Ishimori Koichiro, Goto Yuji, and Lee Young-Ho
  • Journal Title: Langmuir Volume: 32 Issue: 8 Pages: 2010-2022
  • DOI: 10.1021/acs.langmuir.5b03810
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Physicochemical Nature of Interfaces Controlling Ferredoxin NADP+ Reductase Activity through Its Interprotein Interactions with Ferredoxin (2015)
  • Author(s): Kinoshita Misaki, Kim Ju Yaen, Kume Satoshi, Sakakibara Yukiko, Sugiki Toshihiko, Kojima Chojiro, Kurisu Genji, Ikegami Takahisa, Hase Toshiharu, Kimata-Ariga Yoko, Lee Young-Ho
  • Journal Title: Biochimica et Biophysica Acta-Bioenergetics Volume: 1847 Issue: 10 Pages: 1200-1211
  • DOI: 10.1016/j.bbabio.2015.05.023
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The crystal structure of the plant small GTPase OsRacl reveals its mode of binding to NADPH oxidase. (2015)
  • Author(s): Kosami KI, Ohki I, Nagano M, Furuita F, Sugiki T, Kawano Y, Kawasaki T, Fujiwara T, Nakagawa A, Shimamoto K, Kojima C
  • Journal Title: The Journal of Biological Chemistry Volume: 289 Issue: 41 Pages: 28569-78
  • DOI: 10.1074/jbc.m114.603282
  • Description: (in press)(印刷中)
  • Peer Reviewed
• [Journal Article] Utilization of paramagnetic relaxation enhancements for high-resolution NMR structure determination of a soluble loop-rich protein with sparse NOE distance restraints (2015)
  • Author(s): Kyoko Furuita, Saori Kataoka, Toshihiko Sugiki, Yoshikazu Hattori, Naohiro Kobayashi, Takahisa Ikegami, Kazuhiro Shiozaki, Toshimichi Fujiwara and Chojiro Kojima
  • Journal Title: J. Biomol. NMR Volume: 61 Issue: 1 Pages: 55-64
  • DOI: 10.1007/s10858-014-9882-7
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Latest approaches for efficient protein production in drug discovery (2014)
  • Author(s): Toshihiko Sugiki, Toshimichi Fujiwara and Chojiro Kojima
  • Journal Title: Expert Opin. Drug Discov. Volume: 9 Issue: 10 Pages: 1189-1204
  • DOI: 10.1517/17460441.2014.941801
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 核膜タンパク質A型ラミンの電子顕微鏡構造解析 (2015)
  • Author(s): 三尾 宗代、角田 舞、山下 隼人、杉木 俊彦、三尾 和弘
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県、神戸市）
  • Year and Date: 2015-12-02
• [Presentation] ヒト内在性神経保護ペプチドHumaninの立体構造および機能発現に関するNMR解析 (2015)
  • Author(s): 杉木 俊彦、Alsanousi Nesreen1、古板 恭子、藤原 敏道、児嶋 長次郎
  • 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] Scrambling-freeなアミノ酸選択的13C標識法と13C標識の高選択性を利用したアミノ酸選択的 (2015)
  • Author(s): 杉木俊彦、藤原敏道、児嶋長次郎
  • Organizer: 第54回NMR討論会
  • Place of Presentation: 千葉工業大学（千葉県、習志野市）
  • Year and Date: 2015-11-06
• [Presentation] 微生物による組換え蛋白質発現 (2015)
  • Author(s): 杉木俊彦
  • Organizer: 日本蛋白質科学会
  • Place of Presentation: あわぎんホール（徳島県、徳島市）
  • Year and Date: 2015-06-25
  • Invited