Creation of a new scientific field "lipid chemical biology"

• Project/Area Number: 15H03121
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Kyushu University
• Principal Investigator: Matsumori Nobuaki 九州大学, 理学研究院, 教授 (50314357)
• Research Collaborator: Kinoshita Masanao
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2015: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 脂質ケミカルバイオロジー / 脂質 / 膜タンパク質 / 脂質ラフト / 表面プラズモン共鳴 / 蛍光 / 相互作用 / 蛍光脂質 / スフィンゴミエリン / セラミド / ケミカルバイオロジー

Outline of Final Research Achievements

Recent studies demonstrated that lipid molecules interact with membrane proteins and regulate their structures and functions. This makes us to realize the biological significance of lipids. However, due to the lack of conventional method to evaluate the interaction between lipids and membrane proteins, lipid research based on chemical biology has not been fully developed. Hence, in this study, we aimed at the creation of a new research field “lipid chemical biology”. We devised lipid-immobilized beads to identify lipid-specific membrane proteins, developed a SPR-based concise method for quantitative analysis of interaction between lipids and membrane proteins, and synthesized various fluorescent lipids to detect the interaction with membrane proteins using fluorescent microscope. In this way we successfully constructed technical bases for lipid chemical biology research.

Academic Significance and Societal Importance of the Research Achievements

生体膜には数千種に及ぶ多様な脂質が存在するが、脂質膜を形成するためにはこれほど多様な脂質は必要ない。近年、脂質が膜タンパク質と相互作用して膜タンパク質の構造や機能を制御することが示されたことから、それぞれの脂質は膜タンパク質と相互作用して何らかの生理的機能を発揮していると考えられる。本研究で開発した各種方法論を用いることで、脂質と膜タンパク質の相互作用を網羅的に解明できると期待される。これにより、上述の「脂質多様性の意義」という生物学における根源的問いに対する答えを見出すことができる。さらに脂質の生理機能の網羅的解明は、創薬にも繋がる可能性を秘めている。

Research Products

• [Int'l Joint Research] Abo Akademi University(フィンランド)
• [Journal Article] A concise method for quantitative analysis of interactions between lipids and membrane proteins (2019)
  • Author(s): Inada Masataka、Kinoshita Masanao、Sumino Ayumi、Oiki Shigetoshi、Matsumori Nobuaki
  • Journal Title: Analytica Chimica Acta Volume: 1059 Pages: 103-112
  • DOI: 10.1016/j.aca.2019.01.042
  • Peer Reviewed / Open Access
• [Journal Article] Preparation and Membrane Distribution of Fluorescent Derivatives of Ceramide (2019)
  • Author(s): Matsufuji Takaaki、Kinoshita Masanao、Matsumori Nobuaki
  • Journal Title: Langmuir Volume: 35 Issue: 6 Pages: 2392-2398
  • DOI: 10.1021/acs.langmuir.8b03176
  • Peer Reviewed
• [Journal Article] Theonellamide A, a marine-sponge-derived bicyclic peptide, binds to cholesterol in aqueous DMSO: Solution NMR-based analysis of peptide-sterol interactions using hydroxylated sterol (2019)
  • Author(s): Cornelio Kimberly、Espiritu Rafael Atillo、Hanashima Shinya、Todokoro Yasuto、Malabed Raymond、Kinoshita Masanao、Matsumori Nobuaki、Murata Michio、Nishimura Shinichi、Kakeya Hideaki、Yoshida Minoru、Matsunaga Shigeki
  • Journal Title: Biochimica et Biophysica Acta (BBA) - Biomembranes Volume: 1861 Issue: 1 Pages: 228-235
  • DOI: 10.1016/j.bbamem.2018.07.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] On the Importance of the C(1)-OH and C(3)-OH Functional Groups of the Long-Chain Base of Ceramide for Interlipid Interaction and Lateral Segregation into Ceramide-Rich Domains (2018)
  • Author(s): Mouts Anna、Vattulainen Elina、Matsufuji Takaaki、Kinoshita Masanao、Matsumori Nobuaki、Slotte J. Peter
  • Journal Title: Langmuir Volume: 34 Issue: 51 Pages: 15864-15870
  • DOI: 10.1021/acs.langmuir.8b03237
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Sphingomyelin Stereoisomers Reveal That Homophilic Interactions Cause Nanodomain Formation (2018)
  • Author(s): Yano Yo、Hanashima Shinya、Yasuda Tomokazu、Tsuchikawa Hiroshi、Matsumori Nobuaki、Kinoshita Masanao、Al Sazzad Md. Abdullah、Slotte J. Peter、Murata Michio
  • Journal Title: Biophysical Journal Volume: 115 Issue: 8 Pages: 1530-1540
  • DOI: 10.1016/j.bpj.2018.08.042
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evidence of lipid rafts based on the partition and dynamic behavior of sphingomyelins (2018)
  • Author(s): Kinoshita Masanao、Suzuki Kenichi G.N.、Murata Michio、Matsumori Nobuaki
  • Journal Title: Chemistry and Physics of Lipids Volume: 215 Pages: 84-95
  • DOI: 10.1016/j.chemphyslip.2018.07.002
  • Peer Reviewed
• [Journal Article] Synthesis and stereochemical revision of the C31-C67 section of amphidinol 3 (2018)
  • Author(s): Yuma Wakamiya, Makoto Ebine, Mariko Murayama, Hiroyuki Omizu, Nobuaki Matsumori, Michio Murata, Tohru Oishi
  • Journal Title: Angewandte Chemie International Edition Volume: 印刷中 Issue: 21 Pages: 6060-6064
  • DOI: 10.1002/anie.201712167
  • Peer Reviewed / Open Access
• [Journal Article] Synthesis and Complete Structure Determination of a Sperm-Activating and -Attracting Factor Isolated from the Ascidian Ascidia sydneiensis (2018)
  • Author(s): Watanabe Tomohiro、Shibata Hajime、Ebine Makoto、Tsuchikawa Hiroshi、Matsumori Nobuaki、Murata Michio、Yoshida Manabu、Morisawa Masaaki、Lin Shu、Yamauchi Kosei、Sakai Ken、Oishi Tohru
  • Journal Title: Journal of Natural Products Volume: 81 Issue: 4 Pages: 985-997
  • DOI: 10.1021/acs.jnatprod.7b01052
  • Peer Reviewed
• [Journal Article] Dynamic membrane interactions of antibacterial and antifungal biomolecules, and amyloid peptides, revealed by solid-state NMR spectroscopy (2018)
  • Author(s): Naito Akira、Matsumori Nobuaki、Ramamoorthy Ayyalusamy
  • Journal Title: Biochimica et Biophysica Acta (BBA) - General Subjects Volume: 1862 Issue: 2 Pages: 307-323
  • DOI: 10.1016/j.bbagen.2017.06.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 蛍光修飾したスフィンゴミエリン誘導体の脂質ラフト観察への応用 (2018)
  • Author(s): 木下 祥尚, 松森信明
  • Journal Title: 生物物理 Volume: 58 Pages: 321-323
  • NAID: 130007522421
  • Peer Reviewed
• [Journal Article] Recent Solid-State NMR Studies of Hydrated Lipid Membranes (2018)
  • Author(s): Umegawa Yuichi、Matsumori Nobuaki、Murata Michio
  • Journal Title: Annu. Rep. NMR Spectrosc. Volume: 94 Pages: 41-72
  • DOI: 10.1016/bs.arnmr.2017.12.003
  • Peer Reviewed
• [Journal Article] 生体膜を標的にする天然有機化合物 (2018)
  • Author(s): 西村 慎一, 掛谷 秀昭, 松森信明
  • Journal Title: 化学と生物 Volume: 56 Pages: 678-685
  • Peer Reviewed
• [Journal Article] Preparation and Membrane Properties of Oxidized Ceramide Derivatives (2017)
  • Author(s): Matsufuji Takaaki、Kinoshita Masanao、Mouts Anna、Slotte J. Peter、Matsumori Nobuaki
  • Journal Title: Langmuir Volume: 34 Issue: 1 Pages: 465-471
  • DOI: 10.1021/acs.langmuir.7b02654
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Emphatic visualization of sphingomyelin-rich domains by inter-lipid FRET imaging using fluorescent sphingomyelins (2017)
  • Author(s): 1.Kinoshita M, Ano H, Murata M, Shigetomi K, Ikenouchi J, Matsumori N
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 16801-16801
  • DOI: 10.1038/s41598-017-16361-x
  • Peer Reviewed / Open Access
• [Journal Article] The impact of metal complex lipids on viscosity and curvature of hybrid liposomes (2017)
  • Author(s): R. Ohtani, T. Tokita, T. Takaya, K. Iwata, M. Kinoshita, N. Matsumori, M. Nakamura, L. F. Lindoy, S. Hayami
  • Journal Title: Chem. Commun. Volume: 53 Issue: 99 Pages: 13249-13252
  • DOI: 10.1039/c7cc07944c
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Structures of the Largest Amphidinol Homologues from the Dinoflagellate Amphidinium carterae and Structure-Activity Relationships (2017)
  • Author(s): M. Satake, K. Cornelio, S. Hanashima, R. Malabed, M. Murata, N. Matsumori, H. Zhang, F. Hayashi, S. Mori, J. S. Kim, C.-H. Kim, J.-S. Lee
  • Journal Title: Journal of Natural Products Volume: 80 Issue: 11 Pages: 2883-2888
  • DOI: 10.1021/acs.jnatprod.7b00345
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Channel Formation and Membrane Deformation via Sterol-Aided Polymorphism of Amphidinol 3 (2017)
  • Author(s): Iwamoto M, Sumino A, Shimada E, Kinoshita M, Matsumori N, Oiki S
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 10782-10782
  • DOI: 10.1038/s41598-017-11135-x
  • Peer Reviewed / Open Access
• [Journal Article] NMR Studies on Natural Product-Stereochemical Determination and Conformational Analysis in Solution and in Membrane (2017)
  • Author(s): Matsumori Nobuaki、Murata Michio
  • Journal Title: Experimental Approaches of NMR Spectroscopy Volume: - Pages: 383-414
  • DOI: 10.1007/978-981-10-5966-7_14
  • ISBN: 9789811059650, 9789811059667
  • Peer Reviewed
• [Journal Article] Raft-based sphingomyelin interactions revealed by new fluorescent sphingomyelin analogs (2017)
  • Author(s): Masanao Kinoshita, Kenichi GN Suzuki, Nobuaki Matsumori, Misa Takada, Hikaru Ano, Kenichi Morigaki, Mitsuhiro Abe, Asami Makino, Toshihide Kobayashi, Koichiro M Hirosawa, Takahiro K Fujiwara, Akihiro Kusumi, Michio Murata
  • Journal Title: J Cell Biol Volume: 未定 Issue: 4 Pages: 1183-1204
  • DOI: 10.1083/jcb.201607086
  • NAID: 120005998045
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Membrane protein structure determination by SAD, SIR, or SIRAS phasing in serial femtosecond crystallography using an iododetergent (2016)
  • Author(s): Takanori Nakane, Shinya Hanashima, Mamoru Suzuki, Haruka Saiki, Taichi Hayashi, Keisuke Kakinouchi, Shigeru Sugiyama, Satoshi Kawatake, Shigeru Matsuoka, Nobuaki Matsumori, et al
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 113 Issue: 46 Pages: 13039-13044
  • DOI: 10.1073/pnas.1602531113
  • Peer Reviewed / Open Access
• [Journal Article] Sterol-dependent membrane association of the marine sponge-derived bicyclic peptide Theonellamide A as examined by 1H NMR (2016)
  • Author(s): Kimberly Cornelio, Rafael Atillo Espiritu, Yasuto Todokoro, Shinya Hanashima, Masanao Kinoshita, Nobuaki Matsumori, Michio Murata, Shinichi Nishimura, Hideaki Kakeya, Minoru Yoshida, Shigeki Matsunaga
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 24 Issue: 21 Pages: 5235-5242
  • DOI: 10.1016/j.bmc.2016.08.043
  • Peer Reviewed
• [Journal Article] Marine sponge cyclic peptide theonellamide A disrupts lipid bilayer integrity without forming distinct membrane pores. (2016)
  • Author(s): 1.Espiritu, R. A., Cornelio, K., Kinoshita, M., Matsumori, N., Murata, M., Nishimura, S., Kakeya, H., Yoshida, M. & Matsunaga, S.
  • Journal Title: Biochim. Biophys. Acta Volume: 1858 Issue: 6 Pages: 1373-1379
  • DOI: 10.1016/j.bbamem.2016.03.019
  • Peer Reviewed
• [Journal Article] The Structure of the Bimolecular Complex between Amphotericin B and Ergosterol in Membranes Is Stabilized by Face-to-Face van der Waals Interaction with Their Rigid Cyclic Cores (2016)
  • Author(s): Yasuo Nakagawa, Yuichi Umegawa, Naohiro Matsushita, Tomoya Yamamoto, Hiroshi Tsuchikawa, Shinya Hanashima, Tohru Oishi, Nobuaki Matsumori, Michio Murata
  • Journal Title: Biochemistry Volume: 55 Issue: 24 Pages: 3392-3402
  • DOI: 10.1021/acs.biochem.6b00193
  • Peer Reviewed
• [Journal Article] Lipid Interactions and Organization in Complex Bilayer Membranes (2016)
  • Author(s): Engberg, O; Yasuda, T; Hautala, V; Matsumori, N; Nyholm, TKM; Murata, M; Slotte, JP
  • Journal Title: BIOPHYSICAL JOURNAL Volume: 110 Issue: 7 Pages: 1563-1573
  • DOI: 10.1016/j.bpj.2015.12.043
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Formation of Gel-like Nanodomains in Cholesterol-Containing Sphingomyelin or Phosphatidylcholine Binary Membrane As Examined by Fluorescence Lifetimes and H-2 NMR Spectra (2016)
  • Author(s): Yasuda, T; Matsumori, N; Tsuchikawa, H; Lonnfors, M; Nyholm, TKM; Slotte, JP; Murata, M
  • Journal Title: LANGMUIR Volume: 31 Issue: 51 Pages: 13783-13792
  • DOI: 10.1021/acs.langmuir.5b03566
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Role of polyol moiety of amphotericin B in ion channel formation and sterol selectivity in bilayer membrane. (2015)
  • Author(s): Yamamoto, T., Umegawa, Y., Tsuchikawa, H., Matsumori, N., Hanashima, S., Murata, M., Haser, R., Rawlings, B. J., Caffrey, P.
  • Journal Title: Bioorg. Med. Chem. Volume: 23 Issue: 17 Pages: 5782-5788
  • DOI: 10.1016/j.bmc.2015.07.009
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Bioactive Structure of Membrane Lipids and Natural Products Elucidated by a Chemistry-Based Approach (2015)
  • Author(s): Murata, M; Sugiyama, S; Matsuoka, S; Matsumori, N
  • Journal Title: Chemical Record Volume: 15 Issue: 4 Pages: 675-690
  • DOI: 10.1002/tcr.201402097
  • Peer Reviewed
• [Journal Article] Orientation and Order of the Amide Group of Sphingomyelin in Bilayers Determined by Solid-State NMR (2015)
  • Author(s): Matsumori, N; Yamaguchi, T; Maeta, Y; Murata,M
  • Journal Title: BIOPHYSICAL JOURNAL Volume: 108 Issue: 12 Pages: 2816-2824
  • DOI: 10.1016/j.bpj.2015.05.011
  • Peer Reviewed
• [Journal Article] Deuterium NMR of Raft Model Membranes Reveals Domain-Specific Order Profiles and Compositional Distribution (2015)
  • Author(s): Yasuda, T; Tsuchikawa, H; Murata, M; Matsumori, N
  • Journal Title: BIOPHYSICAL JOURNAL Volume: 108 Issue: 10 Pages: 2502-2506
  • DOI: 10.1016/j.bpj.2015.04.008
  • Peer Reviewed
• [Presentation] 脂質間FRETを用いたコントラストの強調とスフィンゴミエリンリッチ領域の可視化 (2019)
  • Author(s): 木下祥尚，阿野光，重富健太，村田道雄，池内順一，松森信明
  • Organizer: 日本化学会第99回春季年会2019
• [Presentation] 低流量電子線散乱法を用いた局所的な脂質充填構造の解析 (2019)
  • Author(s): 山口晋平，木下祥尚， 松森信明
  • Organizer: 日本化学会第99回春季年会2019
• [Presentation] アシル鎖長の異なるスフィンゴミエリンがドメイン形成に与える影響ー蛍光スフィンゴミエリンを用いた検討 (2019)
  • Author(s): 平野佳奈，木下祥尚， 松森信明
  • Organizer: 日本化学会第99回春季年会2019
• [Presentation] 質膜内葉と外葉の非対称性が人工ラフト膜の構造や物性に与える影響 (2019)
  • Author(s): 古閑卓也，木下祥尚，松森信明
  • Organizer: 日本化学会第99回春季年会2019
• [Presentation] 脂質固定ビーズによる脂質特異的タンパク質の同定 (2019)
  • Author(s): 安田裕貴， 松藤嵩明，木下祥尚，松森信明
  • Organizer: 日本化学会第99春季年会
• [Presentation] 工膜脂質に対する吸入麻酔剤の作用 (2019)
  • Author(s): 川口翼，木下祥尚，松森信明
  • Organizer: 日本化学会第99春季年会
• [Presentation] Detailed insight for the effect of specific interaction with lipids on membrane protein activation (2019)
  • Author(s): Masataka Inada，Masanao Kinoshita，Masayuki Iwamoto，Shigetoshi Oiki，Nobuaki Matsumori
  • Organizer: 日本化学会第99春季年会
• [Presentation] Crucial Role of Specific Interactions with Archeal Glycolipid S-TGA-1 in Structuralization and Functionalization of Bacteriorhodopsin (2018)
  • Author(s): Masataka Inada，Masanao Kinoshita，Nobuaki Matsumori
  • Organizer: 第56回日本生物物理学会年会
• [Presentation] 膜タンパク質-脂質相互作用に対する定量評価法の開発および特異的脂質の同定 (2018)
  • Author(s): 稲田壮峰，木下祥尚，松森信明
  • Organizer: 日本分析化学会第67年会
• [Presentation] 異なるアシル鎖をもつ蛍光スフィンゴミエリの調製とドメイン形成の解析 (2018)
  • Author(s): 平野佳奈，木下祥尚，松森信明
  • Organizer: 第12回バイオ関連化学シンポジウム
• [Presentation] 脂質膜中における膜作用性海洋天然物アンフィジノール3とステロールの相互作用 (2018)
  • Author(s): 檜枝愛美， 木下祥尚，松森信明
  • Organizer: 第12回バイオ関連化学シンポジウム
• [Presentation] Development of a concise method for quantitative analysis of interactions between membrane proteins (2018)
  • Author(s): Masataka Inada，Masanao Kinoshita，Nobuaki Matsumori
  • Organizer: International Workshop on Biological Membranes : Tiny Lipids With Grand Function
  • Int'l Joint Research
• [Presentation] NMR and Fluorescent Studies of Lipid Rafts (2016)
  • Author(s): Nobuaki Matsumori and Masanao Kinoshita
  • Organizer: 9th Korea-Japan Seminars on Biomolecular Sciences: Experimental and Simulations
  • Place of Presentation: Gyeongju, Korea
  • Int'l Joint Research / Invited
• [Presentation] 脂質膜における動的挙動、構造および相互作用解析 (2016)
  • Author(s): 松森信明
  • Organizer: 蛋白研セミナー Mechanism of Biology of Membrane: 生体膜上の生物化学
  • Place of Presentation: 吹田
  • Invited
• [Presentation] 脂質ラフト形成基盤の解明を目指したスフィンゴミエリンの動的およびNMR構造解析 (2016)
  • Author(s): 松森 信明
  • Organizer: 日本化学会第96春季年会ケミカルバイオロジーの新機軸ー機器分析とライフイノベーション
  • Place of Presentation: 京田辺
  • Invited
• [Presentation] 脂質ラフトにおける脂質分子の動的挙動および構造解析 (2015)
  • Author(s): 松森信明
  • Organizer: 第88回日本生化学会大会フォーラム
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] 脂質ラフトのNMR解析 (2015)
  • Author(s): 松森信明、村田道雄
  • Organizer: 第53回日本生物物理学会年会
  • Place of Presentation: 金沢
  • Year and Date: 2015-09-13
  • Invited
• [Presentation] NMR studies of lipid rafts (2015)
  • Author(s): Nobuaki Matsumori, Tomokazu Yasuda, Toshiyuki Yamaguchi, Michio Murata
  • Organizer: Pacifichem2015
  • Place of Presentation: Honolulu
  • Int'l Joint Research / Invited
• [Presentation] Small molecule interactions with membrane sterol (2015)
  • Author(s): Pacifichem2015 "Small molecule interactions with membrane sterol" Nobuaki Matsumori, Yuichi Umegawa, Yasuo Nakagawa, Rafael Espiritu, Michio Murata (Honolulu, Dec. 2015)
  • Organizer: Pacifichem2015
  • Place of Presentation: Honolulu
  • Int'l Joint Research / Invited
• [Presentation] 脂質膜の統合分析 (2015)
  • Author(s): 松森信明
  • Organizer: 第33回九州コロイドコロキウム
  • Place of Presentation: 福岡
  • Invited
• [Book] 天然物の化学Ⅱ（科学のとびら64) (2018)
  • Author(s): 上村 大輔 編
  • Total Pages: 192
  • Publisher: 東京化学同人
  • ISBN: 9784807915057
• [Remarks] 九州大学大学院理学研究院化学部門 生体分析化学研究室
  • URL: http://www.scc.kyushu-u.ac.jp/BioanalChem/index.html
• [Remarks] 九州大学大学院理学研究院化学部門 生体分析化学研究室
  • URL: http://www.scc.kyushu-u.ac.jp/BioanalChem/index.html