Exploring the details in LOX-1 ligand recognition mode and its application to diagnosis

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390012
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Hiroshima University
• Principal Investigator: TATE Shin-Ichi Hiroshima University, 大学院・理学研究科, 教授 (20216998)
• Co-Investigator(Kenkyū-buntansha): MACHIDA Sachiko (独)農業・食品産業技術機構, 食品バイオテクノロジー研究領域, ユニット長 (30353981) ; MITSUMORI Fumiyuki (独)国立環境研究所, 化学環境領域, 室長 (90125229)
• Project Period (FY): 2008 – 2010
• Keywords: 構造生物学

Research Abstract

In this project, we found that LOX-1 clustering is essential to exert its specific binding to oxidized LDL (OxLDL). We also revealed that each LOX-1 molecule in the cluster is required to maintain the proper homo-dimeric form, otherwise the clustered LOX-1 do not bind to OxLDL. On the cell surface, LOX-1 clustering was found to be mediated by its preferential localization on the lipid-raft, which localization is regulated by the palmitoylation to two cystein residues in the trans-membrane region. We also devised non-toxic MRI imaging reagent which will be applied to see the location of LOX-1 in vein, which should be the marker for the early-stage atherosclerosis.

Research Products

• [Journal Article] The NMR structure of F1iK, the trigger for the switch of substrate specificity in the flagellar type III secretion apparatus (2011)
  • Author(s): Mizuno, S., Amida, H., Kobayashi, N, Aizawa, S., Tate, S.
  • Journal Title: J.Mol.Biol. in press
  • Peer Reviewed
• [Journal Article] Surface plasmon resonance study on functional significance of clustered organization of lectin-like oxidized LDL (LOX-1) (2011)
  • Author(s): Ohki, I., Amida, H. Yamada, R., Sugihara, M., Ishigaki, T., Tate, S.
  • Journal Title: Biochim et Biophsica Acta 1814 Pages: 345-354
  • Peer Reviewed
• [Journal Article] A region- and stereo-selective parallel synthesis of types of trigalactoses on a solid support as a model of a combinatorial oligosaccharide library (2010)
  • Author(s): Komba, S., Terauchi, T., Machida, S
  • Journal Title: J.App.Glycoscience 58 Pages: 1-12
  • Peer Reviewed
• [Journal Article] Prorine cis/trans isomerase Pinl regulates peroxisome proliferator- activated receptor g activity through the direct binding to the AF-1 domain (2010)
  • Author(s): Fujimoto, Y., Shiraki, T., Horiuchi, Y., Waku, T., Shigenaga, A., Otaka, A., Ikura, T., Igarashi, K., Aimoto, S., Tate, S., Morikawa, K.
  • Journal Title: J.BiolChem. 285 Pages: 3126-3132
  • Peer Reviewed
• [Journal Article] Estimation of brain iron concentration in vivo using a linear relationship between regional iron and apparent transverse relaxation rate of the tissue water at 4.7 T (2009)
  • Author(s): Mitsumori, F., Watanabe, H., Takaya, N.
  • Journal Title: Magn.Reson.Med. 62 Pages: 1326-1330
  • Peer Reviewed
• [Presentation] Alteration to internally correlated motion in protein by the mutation to a loop region (2010)
  • Author(s): Tate, S.
  • Organizer: PachifiChem2010
  • Place of Presentation: Honolulu, Hawaii.
  • Year and Date: 2010-12-18
• [Presentation] Transverse relaxation of the tissue water in human brain in predominantly determined by iron and macromolecules (2009)
  • Author(s): Mitsumori, F.
  • Organizer: The 7th Minnesota Workshop on High-field MRI
  • Place of Presentation: Minnesota, USA.
  • Year and Date: 2009-10-08
• [Book] 広がるNMRの世界(朝倉哲朗編)(章著:タンパク質の分子形態変化観測) (2011)
  • Author(s): 楯真一
  • Total Pages: 46-49
  • Publisher: コロナ社
• [Book] MRの最近の進歩と安全性(日本磁気共鳴医学会)(章著:原理とハードウェアーからMRIの安全を考える) (2008)
  • Author(s): 三森文行
  • Total Pages: 3-13
• [Patent(Industrial Property Rights)] 受容体再構築物,ならびにこれを用いる疾病検査法 (2008)
  • Inventor(s): 町田幸子, 倉持みゆき, 神原祥清, 寺田喜信, 鷹羽武史
  • Industrial Property Rights Holder: 農業・食品産業技術総合研究機構・食品総合研究所
  • Industrial Property Number: 特許・特願,2008-251868
  • Filing Date: 2008-09-29