Structure -Function relationship of Membrane Bound Peptides Using DPC Micelles

具有生物活性的多肽与生物膜结合，发挥膜溶解、膜融合等多种生物学作用。这些活性与嵌入膜中的肽的结构密切相关，这使得我们对结合到膜上的那些肽的三维结构进行了详细的研究。然而，与膜结合的肽通常产生宽的NMR共振，因此我们使用胶束作为模型膜。我们合成了全氘代十二烷基磷酸胆碱，这使得有可能观察到来自肽而不是来自脂质的NMR信号，并且还降低了自旋扩散效应。这些点是使用全氘代胶束的膜结合肽的结构测定的显着优势。我们确定蜂毒肽的结构结合到胶束使用NMR和距离几何计算。Melittin在Prol 4处使用了一根弯曲的杆。但是，弯曲角度无法确定 ...更多信息 d由于缺乏NOE信息。蜂毒肽与膜表面结合，螺旋轴平行于表面。杆的柔性对于膜溶解可能是有效的，就像楔子破坏物体一样。我们还确定了结合到胶束的表皮生长因子（EGF）的三维结构。在这种情况下，胶束模拟受体的疏水环境。EGF与胶束结合的C-末端尾，其中C-末端尾采取两亲性结构。Leu 47被认为是EGF生物活性所必需的。事实上，Leu 47位于连接N端和C端结构域疏水部分的关键位置。EGF的这种两亲性结构对于EGF与受体的结合非常重要。除此之外，我们还对芋螺毒素GIIIA和沙培素等生物活性肽的距离几何计算进行了基础研究，并确定了它们的结构。少

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