M2蛋白是流感病毒的跨膜离子通道， 其跨膜结构域是金刚烷胺等抗流感药物的作用靶标，但过去的十多年时间内产生了大量的耐药性病毒株。针对A型流感病毒的复制传播特点，寻找新的药物作用靶点显得极为迫切。针对M2蛋白羧基末端的功能研究表明，其氨基酸序列相当保守的APH两亲性螺旋在病毒复制的最后出芽释放过程中发挥关键作用。APH以胆固醇依赖的方式作用在病毒出芽的脂筏区，导致质膜发生弯曲，最终完成病毒释放,因此APH很可能成为抗流感药物的新靶点。本研究拟通过nanodiscs及液体核磁共振等技术针对M2的羧基末端APH区段与质膜的相互作用展开研究，通过研究APH与膜相互作用的关键残基、膜磷脂以及胆固醇对于APH介导的病毒出芽的影响等揭示M2蛋白介导病毒出芽的结构基础。研究结果将为针对流感病毒的出芽释放设计筛选新型抗流感药物提供重要结构信息。

Protein M2 from influenza forms a tetrameric proton-selective ion channel，which is the target of the amino-adamantyls. However, the past decade has seen a dramatic increase in resistance to the amino-adamantyls. It is urgent to develop brand-new anti-virus drug. A membrane-interacting amphipathic helix (APH) that is C-terminal to the TMH is important for budding and scission. The APH of M2 binds cholesterol and is proposed to target the protein to the edge of the host cell "budozone". The isolated APH is sufficient for generating curvature in giant unilamellar vesicles, and this activity may facilitate bud formation and scission of nascent virus particles. Here we focus on the interaction between APH and infected cellar membrane by solution NMR and nanodiscs, in order to defining the key sequence of interaction and role of lipid and cholesterol and explaining the principle underling it. The progress will help understanding its structural machanism underlying virus budding and providing structural information for drugs design.