草鱼肠道PepT1对小肽的偏好性转运及机制研究

小肽营养是蛋白质营养的重要组成部分，是饲料行业新的研究热点。小肽转运蛋白PepT1（Oligopeptide transporter 1）在动物小肽营养吸收方面扮演非常重要的角色。前期，我们确认草鱼肠道PepT1对小肽的转运存在偏好性。基于此研究基础，本项目拟进一步研究草鱼肠道PepT1蛋白和小肽结构对小肽转运效率的影响，明确PepT1对小肽的偏好性转运；分析偏好性转运小肽介导上游调控基因对PepT1的调控作用，阐明PepT1对小肽偏好性转运的上游调控机制;通过对PepT1蛋白上小肽关键结合位点的定点突变，研究小肽转运效率及PepT1与小肽相互作用的变化，揭示PepT1对小肽偏好性转运基于结构的分子机制。本项目将为草鱼PepT1的小肽转运研究开启一个新的领域和视角，丰富鱼类肠道小肽吸收及饲料蛋白高效利用的理论基础，并为鱼类饲料配方优化及肽类药物研究与发展提供新的研究思路或方法。

Peptide nutrition is a vital and indispensable part of protein nutrition, also becoming the new hot spot of feed industry. Oligopeptide transporter protein PepT1(Oligopeptide transporter 1) plays a significant role in peptide nutrition absorption of animal. We preliminarily confirmed the existence of preference transportation for intestinal PepT1 to oligopeptides in grass carp in our previous work. Based upon that, this project intends to study the influence of both the structures of PepT1 protein and oligopeptides to translocation efficiency of oligopeptides to ascertain the preference transportation of intestinal PepT1 to oligopeptides; Additionally, preferely transported oligopeptides mediating the regulation of upstream gene to PepT1 would be analyzed to elucidate the upstream regulation mechanism of the preference transportation of PepT1 to oligopeptides. Furthermore, the varieties of the oligopeptide translocation efficiency and interaction of PepT1 with oligopeptides were determined to reveal the molecular mechanism related to PepT1 structure for oligopeptide preference transportation in grass carp by mutations of the key binding site of PepT1 to oligopeptides. This project would uncover a new field and perspective to oligopeptide transportation of intestinal PepT1 in grass carp, enrich the theories foundation of oligopeptide absorption in fish intestine and high efficient utilization of feed, as well as provide new research route or methods to the optimization of fish feed formulation and the research and development of peptide drug.