Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA UK.
School of Chemistry, Cantock's Close, University of Bristol, Bristol BS8 1TS, UK.
Nat Chem. 2017 May;9(5):411-419. doi: 10.1038/nchem.2647. Epub 2016 Nov 14.
The fabrication of monodisperse transmembrane barrels formed from short synthetic peptides has not been demonstrated previously. This is in part because of the complexity of the interactions between peptides and lipids within the hydrophobic environment of a membrane. Here we report the formation of a transmembrane pore through the self-assembly of 35 amino acid α-helical peptides. The design of the peptides is based on the C-terminal D4 domain of the Escherichia coli polysaccharide transporter Wza. By using single-channel current recording, we define discrete assembly intermediates and show that the pore is most probably a helix barrel that contains eight D4 peptides arranged in parallel. We also show that the peptide pore is functional and capable of conducting ions and binding blockers. Such α-helix barrels engineered from peptides could find applications in nanopore technologies such as single-molecule sensing and nucleic-acid sequencing.
以前尚未有研究展示如何制备由短合成肽形成的单分散跨膜桶。这在一定程度上是因为在膜的疏水环境中，肽与脂质之间的相互作用非常复杂。在这里，我们报告了通过 35 个氨基酸α-螺旋肽的自组装形成跨膜孔。这些肽的设计基于大肠杆菌多糖转运蛋白 Wza 的 C 端 D4 结构域。通过使用单通道电流记录，我们定义了离散的组装中间体，并表明该孔很可能是一个包含八个平行排列的 D4 肽的螺旋桶。我们还表明，该肽孔是有功能的，能够传导离子和结合阻断剂。这种由肽设计的α-螺旋桶可应用于纳米孔技术，例如单分子感应和核酸测序。
