Centro de Biología Molecular Severo Ochoa (CSIC/UAM), C/ Nicolás Cabrera, 1, Cantoblanco, 28049 Madrid, Spain.
Biochem Biophys Res Commun. 2012 Mar 30;420(1):42-7. doi: 10.1016/j.bbrc.2012.02.112. Epub 2012 Feb 28.
The fusion of paramyxovirus to the cell membrane is mediated by fusion protein (F protein) present in the virus envelope, which undergoes a dramatic conformational change during the process. Unlike hemagglutinin in orthomyxovirus, this change is not mediated by an alteration of environmental pH, and its cause remains unknown. Steered molecular dynamics analysis leads us to suggest that the conformational modification is mediated only by stretching mechanical forces once the transmembrane fusion peptide of the protein is anchored to the cell membrane. Such elongating forces will generate major secondary structure rearrangement in the heptad repeat A region of the F protein; from β-sheet conformation to an elongated coil and then spontaneously to an α-helix. In addition, it is proposed that the heptad repeat A region adopts a final three-helix coiled coil and that this structure appears after the formation of individual helices in each monomer.
副黏病毒与细胞膜的融合是由病毒包膜中存在的融合蛋白（F 蛋白）介导的，该蛋白在融合过程中经历剧烈的构象变化。与正黏病毒的血凝素不同，这种变化不是由环境 pH 值的改变介导的，其原因尚不清楚。定向分子动力学分析使我们提出，只有在蛋白质的跨膜融合肽锚定在细胞膜上之后，构象修饰才由拉伸机械力介导。这种拉伸力将导致 F 蛋白七肽重复 A 区的主要二级结构重排；从β-折叠构象到拉长的卷曲，然后自发形成α-螺旋。此外，还提出七肽重复 A 区采用最终的三螺旋卷曲结构，并且该结构出现在每个单体的单个螺旋形成之后。
