Composition-dependent membrane disruption by the proapoptotic protein PB1F2 from HK97 influenza A virus
Composition-dependent membrane disruption by the proapoptotic protein PB1F2 from HK97 influenza A virus
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HK97 甲型流感病毒促凋亡蛋白 PB1F2 造成的成分依赖性膜破坏
DOI：
10.1002/1873-3468.13172
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发表时间：
2018
期刊：
影响因子：
3.5
通讯作者：
Junfeng Wang
中科院分区：
文献类型：
--
作者：
Yujuan Wang;Jing Yang;Jiarong Wang;Lei Zhu;Junfeng Wang
PB1F2是甲型流感病毒中由另一个阅读框编码的促凋亡蛋白。它的积聚通过降低线粒体膜电位来加速线粒体的碎裂，但其机制尚不清楚。在此，我们以可溶性形式表达和纯化了HK97的PB1F2。用三种膜模拟物--脂质体、双核细胞和纳米盘研究了PB1F2与线粒体膜的相互作用。我们发现PB1F2和膜模拟物之间的相互作用依赖于脂质类型，并且是时间和剂量依赖的。PB1F2的主要膜靶标是磷脂酰胆碱，磷脂酰胆碱是构成线粒体内膜的主要成分。PB1F2通过形成胶束状的PB1F2-脂质集合体破坏脂膜的完整性。
PB1F2 is a proapoptotic protein encoded by an alternative reading frame in the influenza A virus. Its accumulation accelerates mitochondrial fragmentation by decreasing the mitochondrial membrane potential following translocation into the mitochondrial inner membrane space, but the mechanistic underpinnings remain unclear. Herein, the PB1F2 from HK97 was expressed and purified in soluble form. The interaction between PB1F2 and the mitochondrial membrane were investigated using three membrane mimics, liposomes, bicelles, and nanodiscs. We show that the interactions between PB1F2 and membrane mimics depend on lipid type and are time‐ and dose‐dependent. The primary membrane target of PB1F2 is phosphatidylcholine, the lipid that forms the major component of mitochondrial inner membranes. PB1F2 disrupts the integrity of lipid membranes by forming micelle‐like PB1F2–lipid assemblies.