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A型流感病毒膜质子通道M2是一个重要的抗流感药物靶点,其通道功能与蛋白质构象变化紧密相关.M2跨膜螺旋结构与功能的研究已经取得了显著进展,但其膜内碳端两亲性螺旋的构象变化与M2功能的关系尚不明确.在这个两亲性螺旋中引入能与跨膜域色氨酸形成福斯特共振能量转移(FRET)作用的非天然氨基酸Phe CN,以便研究通道激活或抑制后M2蛋白膜内部分的构象变化.在酸性环境通道激活的条件下,两亲性螺旋与跨膜螺旋间的距离增大,其增大幅度基本不受药物抑制通道活性的影响.由此推测两亲性螺旋的构象变化与通道活性无关,反而很可能与M2在病毒出芽过程中的作用相关.
Influenza A virus membrane proton channel M2 is an important anti-influenza drug target, and its channel function is closely related to the conformational changes of the protein .M2 transmembrane helix structure and function of the research has made significant progress, but its membrane carbon end The relationship between the conformational changes of the parental helix and the function of M2 is unclear, and an unnatural amino acid Phe CN that forms Forster resonance energy transfer (FRET) interaction with the transmembrane domain tryptophan is introduced into this amphipathic helix so that To study the conformational changes of the intramolecular membrane of M2 protein after activation or inhibition of channel.The distance between amphipathic helix and transmembrane helix increases with the activation of acidic environment channel and the increase is basically independent of the activity of drug-suppressed channel It is speculated that the conformational change of amphipathic helix has nothing to do with the activity of the channel, it is likely to be related to the role of M2 in the process of virus budding.