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1991 Fiscal Year Final Research Report Summary

Structure -Function relationship of Membrane Bound Peptides Using DPC Micelles

Research Project

Project/Area Number 02453152
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 物質生物化学
Research InstitutionThe Tokyo Metropolitan Institute of Medical Science

Principal Investigator

INAGAKI Fuyuhiko  The Tokyo Metropolitan Institute of Medical Science, 生理活性物質研究部門, 研究員 (70011757)

Co-Investigator(Kenkyū-buntansha) TATE Shin-ichi  The Tokyo Metropolitan Institute of Medical Science, 生理活性物質研究部門, 研究員 (20216998)
KOHDA Daisuke  The Tokyo Metropolitan Institute of Medical Science, 生理活性物質研究部門, 研究員 (80186618)
Project Period (FY) 1990 – 1991
KeywordsBioactive peptides / Perdeuterated micelles / NMR / Distance geometry
Research Abstract

Biologically active peptides bind to biomembranes and exert several biological actions such as membrane lysis and membrane fusion. These activities are closely related to the structures of the peptides embedded in the membranes, which led us to the detailed investigation of the three dimensional structures of those peptides bound to the membranes. However, the peptides bound to the membranes generally give broad NMR resonances so that we used micelles as model membranes. We synthesized perdeuterated dodecylphosphocholine which made it possible to observe the NMR signals derived from the peptides not from lipids and also reduced the spin diffusion effects. These points are significant advantages of the use of perdeuterated micelles for the structural determination of the membrane bound peptides.
We determined the structure of melittin bound to the micelles using NMR and distance geometry calculations. Melittin takes a rod with a bent at Prol4. However, the bent angle can not be determine … More d due to the lack of NOE information. Melittin binds to the surface of membranes with the helical axis parallel to the surface. The flexibility of the rod may be effective for membrane lysis just as wedges destruct objects. We also determined the three dimensional structure of the epidermal growth factor(EGF)bound to the micelles. In this case, the micelles mimic hydrophobic environments of the receptors. EGF binds to the micelles with the C-terminal tail, where C-terminal tail takes an amphiphilic structure. Leu47 has been suggested to be essential for biological activity of EGF. Actually, Leu47 is located at the pivotal position to connect the hydrophobic parts of the Nterminal and C-terminal domains. This amphiphilic structure of EGF is important for the binding of EGF to the receptor. In addition to these studies, we have made the basic investigation on the distance geometry calculations and determined the structure of biologically active peptides such as yi-conotoxin GIIIA and sapecin. Less

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] T.Ikura: "Refined Structure of Melittin Bound to Perdeuterted Dodecyl-phosphocholine Micelles as Studied by 2D-NMR and Distance Geometry Calculation." Proteins:Structure,Function and Genetics. 9. 81-89 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J-M.Lancelin: "Tertiary Structure of Conotoxin GIIIA in Aqueous Solution" Biochemistry. 30. 6908-6916 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Sato: "Active Site of Conotoxin GIIIA,A Peptide Blocker of Muscle Sodium Channels" J.Biol.Chem.266. 16989-16991 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] D.Kohda: "Characterization of pH Titration Shifts for All the Nonlabile Proton Resonances in a Protein by Two-Dimensional NMR:The Case of Mouse Epidermal Growth Factor," Biochemistry. 30. 4896-4900 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] D.Kohda: "Structure of Epidermal Growth Factor Bound to Perdeuterated Dodecyl-phosphocholine Micelles Determined by Two-Dimensional NMR and Simulated Annealing Calculations," Biochemistry. 31. 677-685 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Ikura, N. Go, F. Inagaki: "Refined Structure of Melittin Bound to Perdeuterated Dodecylphosphocholine Micelles as Studied by 2D-NMR and Distance Geometry Calculation." Proteins : Structure, Function and Genetics. 9. 81-89 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J-M. Lancelin, D. Kohda, S. Tate, Y. Yanagawa, T. Abe, M. Satake, and F. Inagaki: "Tertiary Structure of Conotoxin GIIIA in Aqueous Solution" Biochemistry. 30. 6908-6916 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Sato, Y. Ishida, K. Wakamatsu, R. Kato, H. Honda, Y. Ohizumi H. Nakamura, M. Ohya, J-M. Lancelin, D. Kohda and F. Inagaki: J. Biol. Chem.266. 16989-16991 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] D. Kohda, T. Sawada and F. Inagaki: "Characterization of pH Titration Shifts for All the Nonlabile Proton Resonances in a Protein by Two-Dimensiona NMR : The Case of Epidermal Growth Factor." Biochemistry. 30. 4896-4900 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] D. Kohda and F. Inagaki: "Structure of Epidermal Growth Factor Bound to Perdeuterated Dodecylphosphocholine Micelles Determined by Two-Dimensional NMR and Distance Geometry Calculations." Biochemistry. 31. 677-685 (1992)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-03-16  

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