Structural basis for cell signaling mediated by lipoprotein receptors

2012 Fiscal Year Final Research Report

• Project/Area Number: 22247010
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Osaka University
• Principal Investigator: TAKAGI Junichi 大阪大学, 蛋白質研究所, 教授 (90212000)
• Co-Investigator(Kenkyū-buntansha): IWASAKI Kenji 大阪大学, 蛋白質研究所, 准教授 (20342751) ; NOGI Terukazu 大阪大学, 蛋白質研究所, 助教 (40379102)
• Co-Investigator(Renkei-kenkyūsha): NOGI Terukazu 横浜市立大学, 大学院・生命ナノシステム科学研究科, 准教授 (40379102)
• Project Period (FY): 2010 – 2012
• Keywords: リポ蛋白質受容体 / X線結晶構造解析 / 電子顕微鏡 / エンドサイトーシス

Research Abstract

We have utilized X-ray crystallography and electron microscopy to decipher the structural mechanism underlying signaling through the lipoprotein receptor family proteins. We have gained information about reelin signal transduction in brain development and Wnt signal transduction implicated in cancer and bone formation. Also, we have unraveled a previously undescribed molecular interaction involving LR11 which is implicated in Alzheimer disease

Research Products

• [Journal Article] A point mutation in Semaphorin 4A associates with defective endosomal sorting and causes retinal degeneration (2013)
  • Author(s): Nojima S, Toyofuku T, Kamao H, Ishigami C, Kaneko J, Okuno T, Takamatsu H, Ito D, Kang S, Kimura T, Yoshida Y, Morimoto K, Maeda Y, Ogata A, Ikawa M, Morii E, Aozasa K, Takagi J, Takahashi M, Kumanogoh A.
  • Journal Title: Nature Commun Volume: 4 Pages: 1406
  • DOI: doi:10.1038/ncomms2420
  • Peer Reviewed
• [Journal Article] LDL受容体ファミリーの構造と蛋白質間相互作用 (2012)
  • Author(s): 北郷 悠、高木淳一
  • Journal Title: The Lipid Volume: 23(4) Pages: 56-62
• [Journal Article] Crystal structure of Enpp1, an extracellular glycoprotein involved in bone mineralization and insulin signaling (2012)
  • Author(s): Kato K, Nishimasu H, Okudaira S, Mihara E, Ishitani R, Takagi J, Aoki J, Nureki O
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 109 Pages: 16876-16881
  • DOI: doi:10.1073/pnas.1208017109
  • Peer Reviewed
• [Journal Article] Higher-order architecture of cell adhesion mediated by polymorphic synaptic adhesion molecules neurexin and neuroligin (2012)
  • Author(s): Tanaka, H., Miyazaki, N., Matoba, K., Nogi, T., Iwasaki, K., and Takagi, J
  • Journal Title: Cell Reports Volume: 2(1) Pages: 101-110
  • DOI: doi:10.1016/j.celrep.2012.06.009
  • Peer Reviewed
• [Journal Article] Expression, purification, crystallization and preliminary X-ray crystallographic analysis of Enpp1 (2012)
  • Author(s): Kato K, Nishimasu H, Mihara E, Ishitani R, Takagi J, Aoki J, and Nureki O.
  • Journal Title: Acta Crystallogr. F Volume: 68(7) Pages: 778-782
  • DOI: doi:10.1107/S1744309112019306
  • Peer Reviewed
• [Journal Article] Tilt-angle measurement of a sample stage using a capacitive liquid-based inclinometer (2012)
  • Author(s): Matoba K, Takagi J, Yasunaga T, Jinnai H, Iwasaki K
  • Journal Title: J Electron Microsc Volume: 61(3) Pages: 193-198
  • DOI: doi:10.1093/jmicro/dfs034
  • Peer Reviewed
• [Journal Article] Crystal structure of 5.1 integrin eAtomic details of the fibronectin receptor (2012)
  • Author(s): Nagae, M., Re, S., Mihara, E., Nogi, T., Sugita, Y., and Takagi, J
  • Journal Title: J. Cell Biol Volume: 197(1) Pages: 131-140
  • DOI: doi:10.1083/jcb.201111077
  • Peer Reviewed
• [Journal Article] Functional importance of covalent homodimer of reelin protein linked via its central region (2011)
  • Author(s): Yasui, N., Kitago, Y., Beppu, A., Kohno, T., Morishita, S., Gomi, H., Nagae, M., Hattori, M. and Takagi, J
  • Journal Title: J. Biol. Chem Volume: 286(40) Pages: 35247-35256
  • DOI: doi:10.1074/jbc.M111.242719
  • Peer Reviewed
• [Journal Article] Structural Basis for Variant-Specific Neuroligin-Binding by α-Neurexin (2011)
  • Author(s): Tanaka, H., Nogi, T., Yasui, N., Iwasaki, K. and Takagi, J
  • Journal Title: PLoS One Volume: 6 Pages: e19411
  • DOI: doi:10.1371/journal.pone.0019411
  • Peer Reviewed
• [Journal Article] Crystal structure of Autotaxin, a secreted lysophospholipase D that generates GPCR-signaling lipid mediator (2011)
  • Author(s): Nishimasu, H., Okudaira, S., Hama, K., Mihara, M., Dohmae, N., Ishitani, R., Takagi, J., Aoki, J., Nureki, O
  • Journal Title: Nature Struct. Mol. Biol. Volume: 18 Pages: 205-212
  • DOI: doi:10.1038/nsmb.1998
  • Peer Reviewed
• [Journal Article] Crystallization and preliminary crystallographic analysis of human LR11 Vps10p domain (2011)
  • Author(s): Nakata, Z., Nagae, M., Yasui, N., Bujo, H., Nogi, T., and Takagi, J
  • Journal Title: Acta Crystallographica., F67 Pages: 129-132
  • DOI: doi:10.1107/S1744309110048153
  • Peer Reviewed
• [Journal Article] Structural basis for semaphorin signaling through the plexin receptor (2010)
  • Author(s): Nogi, T., Yasui, N., Mihara, E., Matsunaga, Y., Noda, M., Yamashita, N., Toyofuku, T., Goshima, Y., Kumanogoh, A, and Takagi, J.
  • Journal Title: Nature Volume: 467 Pages: 1123-1127
  • DOI: doi:10.1038/nature09473
  • Peer Reviewed
• [Journal Article] Comparison of the envelope architecture of E. coli using two methods: CEMOVIS and cryo-electron tomography (2010)
  • Author(s): Kishimoto-Okada, A., Murakami, S., Ito, Y., Horii, N., Furukawa, H., Takagi, J., Iwasaki, K
  • Journal Title: J. Electron Microsc Volume: 59 Pages: 419-426
  • DOI: doi:10.1093/jmicro/dfq056
  • Peer Reviewed
• [Presentation] Superimposition of a crystal structure over EM images, KeyStone Symposia (2013)
  • Author(s): Iwasaki, K.
  • Organizer: Structural Analysis of Supramolecular Assemblies by Hybrid Methods
  • Place of Presentation: Lake Tahoe (USA)
  • Year and Date: 2013-03-05
• [Presentation] Multi-faceted approach to analyze structure and function of integrins. (2013)
  • Author(s): Takagi, J
  • Organizer: Gordon Research Conference
  • Place of Presentation: Ventura (USA)
  • Year and Date: 2013-02-14
• [Presentation] In situ molecular analysis by electron microscopy (2012)
  • Author(s): Iwasaki, K
  • Organizer: IPR International Symposium 2012, -Toward the Molecular Comprehension of Life System
  • Place of Presentation: Osaka
  • Year and Date: 2012-11-22
• [Presentation] 蛋白質の立体構造から理解する細胞外シグナル授受のしくみ (2012)
  • Author(s): 高木淳一
  • Organizer: 第12回日本抗加齢医学会 シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2012-06-24
• [Presentation] Wnt共受容体LRP6の電子顕微鏡単粒子解析 (2012)
  • Author(s): 的場京子
  • Organizer: 第12回日本蛋白質科学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-06-21
• [Presentation] Structural basis for peptide ligand recognition by LR11/sorLA Vps10p domain (2012)
  • Author(s): Takagi, J
  • Organizer: Keystone Symposia "ApoE, Alzheimer's and Lipoprotein Biology"
  • Place of Presentation: Key Stone (USA)
  • Year and Date: 2012-02-28
• [Presentation] LR11 Vps10pドメインのリガンド認識機構 (2011)
  • Author(s): 北郷 悠 他
  • Organizer: 2011年度日本結晶学会年会
  • Place of Presentation: 札幌
  • Year and Date: 2011-11-24
• [Presentation] リーリンN末端断片の精製及び結晶化 (2011)
  • Author(s): 長江 雅倫 他
  • Organizer: 2011年度日本結晶学会年会
  • Place of Presentation: 札幌
  • Year and Date: 2011-11-24
• [Presentation] ソーティング受容体LR11の持つ"弱くて特異性の低い (2011)
  • Author(s): 高木淳一
  • Organizer: 相互作用の秘密、第2回 「神経科学と構造生物学の融合」セミナー
  • Place of Presentation: 岡崎
  • Year and Date: 2011-11-21
• [Presentation] Structural basis for peptide ligand recognition by LR11 Vps10p domain (2011)
  • Author(s): Kitago, Y. et al
  • Organizer: PDB40 symposium
  • Place of Presentation: New York (USA)
  • Year and Date: 2011-10-28
• [Presentation] 脳の層構造形成を制御するリーリンシグナルの分子機構 (2011)
  • Author(s): 禾 晃和
  • Organizer: 蛋白質研究所セミナー・細胞表面受容体と細胞内輸送
  • Place of Presentation: 大阪
  • Year and Date: 2011-01-12
• [Presentation] Structural and functional analysis of LR11 Vps10p domain (2010)
  • Author(s): Nakata, Z., Takagi, J. et al
  • Organizer: American Crystallographic Association
  • Place of Presentation: Chicago(USA)
  • Year and Date: 2010-07-25
• [Book] タンパク質間相互作用の検出-表面プラズモン共鳴法、「タンパク質実験ノート(下)」(岡田雅人、三木裕明、宮崎 香 編) (2011)
  • Author(s): 寒川 剛、高木淳一
  • Total Pages: 132-137
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.protein.osaka-u.ac.jp/rcsfp/synthesis/index.html
• [Patent(Industrial Property Rights)] タグペプチド及びその利用 (2013)
  • Inventor(s): 高木淳一
  • Industrial Property Rights Holder: 国立大学法人大阪大学
  • Industrial Property Number: 特許第5257997号
  • Acquisition Date: 2013-05-02
• [Patent(Industrial Property Rights)] TAG PEPTIDE HAVING A PROTEASE RECOGNITION SEQUENCE AND USE THEREOF (2012)
  • Inventor(s): 高木淳一
  • Industrial Property Rights Holder: 国立大学法人大阪大学
  • Industrial Property Number: 13/265,024
  • Acquisition Date: 2012-12-26
  • Overseas