Side chain effect on ion channel characters of Aib rich peptides
Side chain effect on ion channel characters of Aib rich peptides
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DOI：
10.1093/oxfordjournals.jbchem.a003045
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发表时间：
2001-12-01
影响因子：
2.7
通讯作者：
Kondo, M
中科院分区：
文献类型：
--
作者：
Hara, T;Kodama, H;Kondo, M
作为离子通道蛋白和天然造孔肽的模型，我们设计了一系列富含AIB的多肽[Ac-(AIB-xxx-AIB-Ala)(5)-NH2(xxx=Lys，Glu，Ser，and Gly：BXBA-20)]，以研究氨基酸残基Lys，Glu，Ser和Gly的侧链对离子通道构象和电生理性质的影响。用圆二色谱评价了多肽的构象及其与磷脂膜的亲和力。膜片钳实验表明，所有的BXBA-20多肽都在DPhPC双层膜中形成离子通道，表现出明显的开放和关闭状态之间的转换。通道形成频率顺序为BKBA-20>；BEBA-20>；BSBA-20>；BGBA-20。在BIKBA-20和BEBA-20的情况下，自组装的导电低聚物表现出均匀的和电压无关的单通道电导。相反，在相似的实验条件下，在BSBA-20和BGBA-20离子通道中观察到了不均匀的电导。这些结果表明，具有高度螺旋构象、高两亲性、对脂膜亲和力高、囊泡具有自缔合特性的多肽最适合于诱导出现频率较高的离子通道。此外，BEBA-20、BSBA-20和BGBA-20通道是阳离子选择性的，而BEBA-20通道是非选择性的。
As models of ion channel proteins and naturally occurring pore-forming peptides, we designed a series of Aib rich peptides [Ac-(Aib-XXx-Aib-Ala)(5)-NH2 (Xxx = Lys, Glu, Ser, and Gly: BXBA-20)] to investigate the effects of the side chains of the amino acid residues Lys, Glu, Ser, and Gly on the conformation and electrophysiological properties of ion channels. The conformation of peptides and their affinity for phospholipid membranes were evaluated by CD spectroscopy. Patch-clamp experiments revealed that all BXBA-20 peptides form ion channels in DPhPC bilayers exhibiting clearly resolved transitions between the open and closed states. The channel forming frequency was in the order BKBA-20 > BEBA-20 > BSBA-20 > BGBA-20. In the case of BIKBA-20 and BEBA-20, the self-assembled conductive oligomers expressed homogeneous and voltage-independent single channel conductances. In contrast, heterogeneous conductance was observed in BSBA-20 and BGBA-20 ion channels under similar experimental conditions. From these results, we conclude that peptides with a high degree of helical conformation, high amphipathicity, high affinity for lipid membranes, and self-associating characters in vesicles are most suitable for inducing ion channels with a high frequency of occurrence. Moreover, BEBA-20, BSBA-20, and BGBA-20 channels were cation-selective, whereas the BEBA-20 channel was non-selective.