Characterization of conformational dynamics of the active end of amyloid fibril to elucidate mechanisms underlying the fibril elongation

2012 Fiscal Year Final Research Report

• Project/Area Number: 23870043
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Biophysics
• Research Institution: 大学共同利用機関法人自然科学研究機構(岡崎共通研究施設) (2012); National Institutes of Natural Sciences Okazaki Research Facilities (2011)
• Principal Investigator: YAGI Maho 大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 岡崎統合バイオサイエンスセンター, 特任助教 (40608999)
• Project Period (FY): 2011 – 2012
• Keywords: アミロイド / アルツハイマー病 / 抗体 / NMR

Research Abstract

To characterize the conformational dynamics of the active end of amyloid fibril, we attempted to design small-sized amyloid fibril models. We successfully prepared tandem repeats of amyloid β (Aβ) molecules as minimal models of the amyloid fibrils by genetic manipulation. It was revealed that the tandem-repeat Aβ was recognized by the specific antibody directed against the end point of Aβ amyloid fibrils and served as nucleus which promoted the amyloid fibrillization. Furthermore, we found that bacterial molecular chaperones and ganglioside-embedding bicelles could suppress formation of Aβ fibrils.

Research Products

• [Journal Article] NMR characterization of the interaction of GroEL with amyloid β as a model ligand (2013)
  • Author(s): Maho Yagi-Utsumi, Tomoko Kunihara, Takashi Nakamura, Yoshinori Uekusa, Koki Makabe, Kunihiro Kuwajima, Koichi Kato.
  • Journal Title: FEBS Lett Volume: 587 Pages: 1605-1609
  • DOI: DOI: 10.1016/j.febslet.2013.04.007
  • Peer Reviewed
• [Journal Article] Nuclear magnetic resonance approaches for characterizing interactions between the bacterial chaperonin GroEL and unstructured proteins. (2013)
  • Author(s): Noritaka Nishida, Maho Yagi-Utsumi, Fumihiro Motojima, Masasuke Yoshida, Ichio Shimada, Koichi Kato
  • Journal Title: J. Biosci. Bioeng. Volume: (in press)
  • DOI: DOI: pii: S1389-1723(13)00054-6. 10.1016/j.jbiosc.2013.02.012.
  • Peer Reviewed
• [Journal Article] Structural and functional mosaic nature of MHC class I molecules in their peptide-free form (2013)
  • Author(s): Eiji Kurimoto, Kimiko Kuroki, Yoshiki Yamaguchi, Maho Yagi-Utsumi, Takahiro Igaki, Takeshi Iguchi, Katsumi Maenaka, Koichi Kato.
  • Journal Title: Molecular Immunology Volume: 55 Pages: 393-399
  • DOI: DOI: 10.1016/j.molimm.2013.03.014.
  • Peer Reviewed
• [Journal Article] The use of spin desalting columns in DMSO-quenched H/D-exchange NMR experiments (2013)
  • Author(s): Mahesh S. Chandak, Takashi Nakamura, Toshio Takenaka, Tapan K. Chaudhuri, Maho Yagi-Utsumi, Jin Chen, Koichi Kato, Kunihiro Kuwajima
  • Journal Title: Protein Science Volume: 22 Pages: 486-491
  • DOI: DOI: 10.1002/pro.2221.
  • Peer Reviewed
• [Journal Article] Solution structure of the Q41N variant of ubiquitin as a model for the alternatively folded N2 state of ubiquitin (2013)
  • Author(s): Soichiro Kitazawa, Tomoshi Kameda, Maho Yagi-Utsumi, Kenji Sugase, Nicola J. Baxter, Koichi Kato, Michael P. Williamson, Ryo Kitahara.
  • Journal Title: Biochemistry Volume: 52 Pages: 1874-1885
  • DOI: DOI: 10.1021/bi301420m.
  • Peer Reviewed
• [Journal Article] Stable isotope-assisted NMR characterization of interaction between lipid A and sarcotoxin IA, a cecropin-type antibacterial peptide. Biochem. Biophys (2013)
  • Author(s): Maho Yagi-Utsumi, Yoshiki Yamaguchi, Pornthip Boonsri, Takeshi Iguchi, Kazuo Okemoto, Shunji Natori, Koichi Kato
  • Journal Title: Res. Commun Volume: 431 Pages: 136-140
  • DOI: DOI: 10.1016/j.bbrc.2013.01.009.
  • Peer Reviewed
• [Journal Article] Ganglioside-embedding small bicelles for probing membrane-landing processes of intrinsically disordered proteins. (2013)
  • Author(s): Takumi Yamaguchi, Tsuyoshi Uno, Yoshinori Uekusa, Maho Yagi-Utsumi, Koichi Kato.
  • Journal Title: Chem. Commun Volume: 49 Pages: 1235-1237
  • DOI: DOI: 10.1039/c2cc38016a.
  • Peer Reviewed
• [Journal Article] Susumu Uchiyama, Koichi Kato, Makoto Fujita. Protein encapsulation within synthetic molecular hosts (2012)
  • Author(s): Daishi Fujita, Kosuke Suzuki, Sato Sota, Maho Yagi-Utsumi, Yoshiki Yamaguchi, Nobuhiro Mizuno, Takashi kumasaka, Masaki Takata, Nasanori Noda
  • Journal Title: Nature Communications Volume: 3 Pages: 1093
  • DOI: DOI: 10.1038/ncomms2093
  • Peer Reviewed
• [Journal Article] NMR and mutational identification of the collagen-binding site of the chaperone Hsp47. (2012)
  • Author(s): Maho Yagi-Utsumi, Sumi Yoshikawa, Yoshiki Yamaguchi, Yohei Nishi, Eiji Kurimoto, Yoshihito Ishida, Takayuki Homma, Jun Hoseki, Yoshimi Nishikawa, Takaki Koide, Kazuhiro Nagata, Koichi Kato.
  • Journal Title: PLoS One Volume: 7 Pages: e45930
  • DOI: DOI: 10.1371/journal.pone.0045930.
  • Peer Reviewed
• [Journal Article] A non-canonical UBA-UBL interaction forms the linear-ubiquitin-chain assembly complex (2012)
  • Author(s): Hirokazu Yagi, Kazuhiro Ishimoto, Takeshi Hiromoto, Hiroaki Fujita, TsunehiroMizushima, Yoshinori Uekusa, Maho Yagi-Utsumi, Eiji Kurimoto, Masanori Noda, Susumu Uchiyama, Fuminori Tokunaga, Kazuhiro Iwai and Koichi Kato.
  • Journal Title: EMBO reports Volume: 13 Pages: 462-468
  • DOI: DOI: 10.1038/embor.2012.24.
  • Peer Reviewed
• [Journal Article] Expression and purification of isotopicaly labeled amyloid β as ubiquitin-fused protein in E. coli (2012)
  • Author(s): Maho Yagi-Utsumi
  • Journal Title: Protein Science Society of Japan Archives, Volume: 5 Pages: e065
  • URL: http://www.pssj.jp/archives/Protocol/Expression/amy_02/amy_02_01.html
  • Peer Reviewed
• [Journal Article] Structural and molecular basis of carbohydrate-protein interaction systems as potential therapeutic targets. (2011)
  • Author(s): Yukiko Kamiya, Maho Yagi-Utsumi, Hirokazu Yagi, and Koichi Kato
  • Journal Title: Current Pharmaceutical Design Volume: 17 Pages: 1672-1684
  • DOI: DOI: 10.2174/138161211796355074
  • Peer Reviewed
• [Presentation] NMR approaches for characterizing molecular recognition process of intrinsically disordered proteins, Fifth Korea-Japan Seminars on Biomolecular Sciences (2013)
  • Author(s): Maho Yagi-Utsumi, Takumi Yamaguchi,Yoshinori Uekusa Koichi Kato.
  • Organizer: Experiments and Simulations
  • Place of Presentation: High1 Resort (Korea)
  • Year and Date: 2013-02-25
• [Presentation] NMR spectroscopic characterization of the pathogenic interaction of amyloid β peptide with GM1 clusters (2013)
  • Author(s): Maho Yagi-Utsumi, Koichi Kato
  • Organizer: Pure and Applied Chemistry International Conference 2013 (PACCON 2013)
  • Place of Presentation: Bangsaen Beach(Thailand)
  • Year and Date: 2013-01-24
• [Presentation] NMR法による神経変性疾患関連タンパク質とガングリオシドクラスターとの相互作用解析 (2012)
  • Author(s): 矢木真穂、山口拓実、植草義徳、加藤晃一
  • Organizer: 第34回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 京都大学薬学部(京都)
  • Year and Date: 2012-11-16
• [Presentation] Conformational transition and intermolecular interaction of amyloid β molecules promoted on ganglioside clusters (2011)
  • Author(s): Maho Yagi-Utsumi, Koichi Kato
  • Organizer: The International Symposium on Nuclear Magnetic Resonance 2011
  • Place of Presentation: 大さん橋ホール(神奈川)
  • Year and Date: 2011-11-16
• [Presentation] NMR characterization of interaction modes of amyloid β with ganglioside clusters (2011)
  • Author(s): Maho Yagi-Utsumi, Koichi Kato
  • Organizer: 3rd Asian Communications of Glycobiology and Glycotechnology
  • Place of Presentation: Shanghai Institute of Organic Chemistry(China)
  • Year and Date: 2011-10-27
• [Presentation] ガングリオシドクラスターが誘起するアミロイドβ重合の開始機構の解明 (2011)
  • Author(s): 矢木真穂、加藤晃一
  • Organizer: 第30回 日本糖質学会年会
  • Place of Presentation: ハイブ長岡(新潟)
  • Year and Date: 2011-07-12
• [Presentation] ガングリオシドクラスターを舞台とするアミロイドβの構造転移と分子間相互作用 (2011)
  • Author(s): 矢木真穂、加藤晃一
  • Organizer: 第11回日本蛋白質科学会
  • Place of Presentation: ホテル阪急エキスポパーク(大阪)
  • Year and Date: 2011-06-08
• [Remarks]
  • URL: http://www.ims.ac.jp/topics/2010/110217.html