多肽与钾离子通道跨膜螺旋S1-S2细胞外linker新型的作用与机制研究

不同钾通道跨膜螺旋S1-S2细胞外linker具有非常显著的序列多样性，几十年来它们结构与功能关系是一个长期冬眠的基础科学问题。立足我们多肽与钾通道作用研究的系统工作积累，及基于防御素多肽初步揭开这个问题神秘面纱的新发现（J-Biol-Chem,2015,290:15487; FASEB-J,2015,29: 4324），本项目紧紧围绕“多肽与钾通道跨膜螺旋S1-S2细胞外linker的作用与机制”关键科学问题，系统开展作用钾通道跨膜螺旋S1-S2细胞外linker多肽的筛选与鉴定，深入研究多肽与钾通道跨膜螺旋S1-S2细胞外linker分子作用机制，分子设计特异性作用钾通道跨膜螺旋S1-S2细胞外linker多肽。这些工作不仅将首次发现众多结构多样的新型功能多肽，而且将创新地揭示钾通道跨膜螺旋S1-S2细胞外linker结构功能的多样性，开辟多肽与钾通道相互作用与生物医药应用的新领域。

The extracellular linkers between transmembrane helices S1 and S2 (S1-S2 linker) in various potassium channels are full of sequence diversity, however, their structure-function relationships remain unknown for a long time. Based on the our systematic work on peptide-potassium channel interactions, we first fortunately unmasked the veil of potassium channel S1-S2 linkers through using human defensin peptides (J Biol Chem, 2015, 290: 15487; FASEB J, 2015, 29: 4324).This project will focus on the novel interactions and mechanisms between peptides and potassium channel S1-S2 linkers, and carry out following studies: screening and identifying peptides interacting with potassium channel S1-S2 linkers; in-depth investigating molecular mechanisms on peptide-potassium channel S1-S2 linker interactions; designing selective and potent peptides acting on the S1-S2 linkers of potassium channels. These work will not only find more and structurally diverse peptides interacting with potassium channel S1-S2 linkers, but also reveal the structural and funcitonal diversity of potassium channel S1-S2 linkers, and open a new field on the interactions and bio-medical applications on peptides and their receptors of potassium channel S1-S2 linkers in the future.