苏州大学药学院,苏州大学药学院
国家自然科学基金青年科学基金资助项目(81402902)
College of Pharmaceutical Sciences,Soochow University,College of Pharmaceutical Sciences,Soochow University;China
This work was supported by a grant from The National Natural Science Foundation of China (81402902)
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PheCN,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.
The influenza A virus M2 proton channel, is the target of anti-flu medications, amantadine and rimantadine. The functions of M2 is closely related to its conformation changes. While extensive progresses have been made regarding the structure-function relationship for the transmembrane helix, there have been much fewer studies for the other membrane associated segment, the C-terminal amphiphilic helix. We carried out FRET experiments by introducing into the amphiphilic helix an unnatural amino acid, PheCN, as the donor for the W residue located in the transmembrane helix. This allowed us to study the global conformation change of these membrane associated structures under channel activation or drug inhibition. The distance between amphipathic helix and transmembrane helix increased upon channel activation in the acidic environment. The degree of this distance increase was not affected by drug inhibition. Therefore we speculate that the conformation change of amphipathic helix is not related to the proton channel activity, but is more likely associated with the protein’s role in virus budding.
李俊北,仇晓琰. A型流感病毒M2膜蛋白两亲性螺旋构象变化的FRET研究[J].生物化学与生物物理进展,2016,43(8):796-800
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