Amino acid sequence requirements of the transmembrane and cytoplasmic domains of influenza virus hemagglutinin for viable membrane fusion
Amino acid sequence requirements of the transmembrane and cytoplasmic domains of influenza virus hemagglutinin for viable membrane fusion
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DOI：
10.1091/mbc.10.6.1821
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发表时间：
1999-06-01
影响因子：
3.3
通讯作者：
Cohen, FS
中科院分区：
文献类型：
--
作者：
Melikyan, GB;Lin, SS;Cohen, FS
研究了流感病毒血凝素（HA）跨膜区（TM）和胞质尾区（CT）在膜融合中的氨基酸序列要求。将野生型HA的融合特性与由HA的胞外域和多聚免疫球蛋白受体（一种非病毒整合膜蛋白）的TM结构域和/或CT组成的嵌合体的融合特性进行比较。融合不需要CT。但是当存在TM结构域和CT时，当它们来源于相同蛋白质时的融合活性大于来源于不同蛋白质时的融合活性。事实上，具有HA的TM结构域和多聚免疫球蛋白受体的截短CT的嵌合体不支持完全融合，表明这两个区域在功能上不是独立的。尽管事实上TM结构域的序列中存在支持融合的宽的自由度，但是HA的TM结构域内的一个保守残基的点突变抑制融合。外源TM结构域支持融合的能力与孔仅由融合蛋白组成的假设相矛盾，并支持TM结构域在半融合阶段完成后产生融合孔的理论。
The amino acid sequence requirements of the transmembrane (TM) domain and cytoplasmic tail (CT) of the hemagglutinin (HA) of influenza virus in membrane fusion have been investigated. Fusion properties of wild-type HA were compared with those of chimeras consisting of the ectodomain of HA and the TM domain and/or CT of polyimmunoglobulin receptor, a nonviral integral membrane protein. The presence of a CT was not required for fusion. But when a TM domain and CT were present, fusion activity was greater when they were derived from the same protein than derived from different proteins. In fact, the chimera with a TM domain of HA and truncated CT of polyimmunoglobulin receptor did not support full fusion, indicating that the two regions are not functionally independent. Despite the fact that there is wide latitude in the sequence of the TM domain that supports fusion, a point mutation of a semiconserved residue within the TM domain of HA inhibited fusion. The ability of a foreign TM domain to support fusion contradicts the hypothesis that a pore is composed solely of fusion proteins and supports the theory that the TM domain creates fusion pores after a stage of hemifusion has been achieved.