Sammalkorpi M, Lazaridis T
Department of Chemistry, City College of the City University of New York, NY 10031, USA.
Biochim Biophys Acta. 2007 Jan;1768(1):30-8. doi: 10.1016/j.bbamem.2006.08.008. Epub 2006 Aug 22.
The 20 N-terminal residues of the HA2 subunit of influenza hemagglutinin (HA), known as the fusion peptide, play a crucial role in membrane fusion. Molecular dynamics simulations with implicit solvation are employed here to study the structure and orientation of the fusion peptide in membranes. As a monomer the alpha-helical peptide adopts a shallow, slightly tilted orientation along the lipid tail-head group interface. The average angle of the peptide with respect to membrane plane is 12.4 degrees . We find that the kinked structure proposed on the basis of NMR data is not stable in our model because of the high energy cost related to the membrane insertion of polar groups. Because hemagglutinin-mediated membrane fusion is promoted by low pH, we examined the effect of protonation of the Glu and Asp residues. The configurations of the protonated peptides were slightly deeper in the membrane but at similar angles. Finally, because HA is a trimer, we modeled helical fusion peptide trimers. We find that oligomerization affects the insertion depth of the peptide and its orientation with respect to the membrane: a trimer exhibits equally favorable configurations in which some or all of the helices in the bundle insert obliquely deep into the membrane.
流感血凝素（HA）的HA2亚基的20个N端残基，即融合肽，在膜融合中起关键作用。本文采用隐式溶剂化的分子动力学模拟来研究膜中融合肽的结构和取向。作为单体，α-螺旋肽沿着脂质尾-头基团界面采取浅的、略微倾斜的取向。肽相对于膜平面的平均角度为12.4度。我们发现，基于核磁共振数据提出的扭结结构在我们的模型中不稳定，因为与极性基团插入膜相关的能量成本很高。由于低pH促进血凝素介导的膜融合，我们研究了Glu和Asp残基质子化的影响。质子化肽的构型在膜中略深，但角度相似。最后，由于HA是三聚体，我们对螺旋融合肽三聚体进行了建模。我们发现寡聚化会影响肽的插入深度及其相对于膜的取向：三聚体表现出同样有利的构型，其中束中的一些或所有螺旋倾斜地深入插入膜中。
