Structure -Function relationship of Membrane Bound Peptides Using DPC Micelles
| Project/Area Number |
02453152
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
物質生物化学
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| Research Institution | The Tokyo Metropolitan Institute of Medical Science |
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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)
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| 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)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1991: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1990: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Keywords | Bioactive peptides / Perdeuterated micelles / NMR / Distance geometry / 膜融合性ペプチド / 構造ー機能相関 |
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| 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
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Report
(3 results)
Research Products
(17 results)
