School of Biosciences and Biotechnology, University of Camerino, 62032, Camerino, Italy.
Division of Innate Immunity, Department of Microbiology and Immunology, The University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo, 108 8639, Japan.
Sci Rep. 2017 Oct 13;7(1):13169. doi: 10.1038/s41598-017-13709-1.
Wheat amylase/trypsin bi-functional inhibitors (ATIs) are protein stimulators of innate immune response, with a recently established role in promoting both gastrointestinal and extra-gastrointestinal inflammatory syndromes. These proteins have been reported to trigger downstream intestinal inflammation upon activation of TLR4, a member of the Toll-like family of proteins that activates signalling pathways and induces the expression of immune and pro-inflammatory genes. In this study, we demonstrated the ability of ATI to directly interact with TLR4 with nanomolar affinity, and we kinetically and structurally characterized the interaction between these macromolecules by means of a concerted approach based on surface plasmon resonance binding analyses and computational studies. On the strength of these results, we designed an oligopeptide capable of preventing the formation of the complex between ATI and the receptor.
小麦淀粉酶/胰蛋白酶双功能抑制剂（ATIs）是先天免疫反应的蛋白刺激物，最近在促进胃肠道和胃肠外炎症综合征方面发挥了作用。这些蛋白质被报道在激活 Toll 样家族蛋白之一的 TLR4 后引发下游肠道炎症，该蛋白激活信号通路并诱导免疫和促炎基因的表达。在这项研究中，我们证明了 ATI 以纳摩尔亲和力直接与 TLR4 相互作用的能力，并通过基于表面等离子体共振结合分析和计算研究的协同方法，对这些大分子之间的相互作用进行了动力学和结构表征。基于这些结果，我们设计了一种能够阻止 ATI 与受体形成复合物的寡肽。
