Tsurudome Masato, Ohtsuka Junpei, Ito Morihiro, Nishio Machiko, Nosaka Tetsuya
Department of Microbiology and Molecular Genetics, Graduate School of Medicine, Mie University, Tsu, Japan.
Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai, Japan.
Front Microbiol. 2018 Mar 13;9:391. doi: 10.3389/fmicb.2018.00391. eCollection 2018.
Membrane fusion by the parainfluenza viruses is induced by virus-specific functional interaction between the attachment protein (HN) and the fusion (F) protein. This interaction is thought to be mediated by transient contacts between particular amino acids in the HN stalk domain and those in the F head domain. However, we recently reported that replacement of specified amino acids at or around the dimer interface of the HN head domain remarkably affected the F protein specificity. We then intended to further investigate this issue in the present study and revealed that the HPIV2 HN protein can be converted to an SV41 HN-like protein by substituting at least nine amino acids in the HPIV2 HN head domain with the SV41 HN counterparts in addition to the replacement of the stalk domain, indicating that specified amino acids in the HN head domain play very important roles in determining the specificity of the HN-F interaction. On the other hand, we previously reported that the PIV5 F protein can be converted to an SV41 F-like protein by replacing 21 amino acids in the head domain of the PIV5 F protein with those of the SV41 F protein. We then intended to further investigate this issue in the present study and found that replacement of 15 amino acids in the stalk domain in addition to the replacement of the 21 amino acids in the head domain of the PIV5 F protein resulted in creation of a more SV41 F-like protein, indicating that specified amino acids in the F stalk domain play important roles in determining the specificity of the HN-F interaction. These results suggest that the conformations of the HN stalk domain and the F head domain are dependent on the structures of the HN head domain and the F stalk domain, respectively. Presumably, the conformations of the former domains, which are considered directly involved in the HN-F interaction, can be modified by subtle changes in the structure of the latter domains, resulting in an altered specificity for the interacting partners.
副流感病毒的膜融合是由附着蛋白（HN）与融合蛋白（F）之间病毒特异性的功能相互作用所诱导的。这种相互作用被认为是由HN柄结构域中特定氨基酸与F头部结构域中特定氨基酸之间的瞬时接触介导的。然而，我们最近报道，在HN头部结构域二聚体界面处或其周围替换特定氨基酸会显著影响F蛋白的特异性。然后，我们打算在本研究中进一步探讨这个问题，并发现除了替换柄结构域之外，通过用SV41 HN对应氨基酸替换HPIV2 HN头部结构域中至少九个氨基酸，HPIV2 HN蛋白可以转化为类似SV41 HN的蛋白，这表明HN头部结构域中的特定氨基酸在决定HN-F相互作用的特异性方面起着非常重要的作用。另一方面，我们之前报道，通过用SV41 F蛋白的氨基酸替换PIV5 F蛋白头部结构域中的21个氨基酸，PIV5 F蛋白可以转化为类似SV41 F的蛋白。然后，我们打算在本研究中进一步探讨这个问题，并发现除了替换PIV5 F蛋白头部结构域中的21个氨基酸之外，替换柄结构域中的15个氨基酸会产生一个更类似SV41 F的蛋白，这表明F柄结构域中的特定氨基酸在决定HN-F相互作用的特异性方面起着重要作用。这些结果表明，HN柄结构域和F头部结构域的构象分别依赖于HN头部结构域和F柄结构域的结构。据推测，被认为直接参与HN-F相互作用的前一个结构域的构象可以通过后一个结构域结构的细微变化而改变，从而导致与相互作用伙伴的特异性改变。
