Institute of Physics, Polish Academy of Sciences, Lotników 32/46 Avenue, 02-668 Warsaw, Poland.
Centre of New Technologies, University of Warsaw, Banacha 2C Street, 02-097 Warsaw, Poland.
Int J Mol Sci. 2018 Feb 14;19(2):578. doi: 10.3390/ijms19020578.
Cleavage of hemagglutinin precursor (HA0) by cellular proteases results in the formation of two subunits, HA1 and HA2. The N-terminal fragment of HA2, named a fusion peptide (HAfp), possess a charged, amine N-terminus. It has been shown that the N-terminus of HAfp stabilizes the structure of a helical hairpin observed for a 23-amino acid long peptide (HAfp1-23), whose larger activity than HAfp1-20 has been demonstrated recently. In this paper, we analyze the effect of N-terminal charge on peptide-mediated fusion efficiency and conformation changes at the membrane interface by comparison with the corresponding -acetylated peptides of 20- and 23-amino acid lengths. We found that higher fusogenic activities of peptides with unmodified amino termini correlates with their ability to form helical hairpin structures oriented perpendicularly to the membrane plane. Molecular dynamics simulations showed that acetylated peptides adopt open and surface-bound conformation more often, which induced less disorder of the phospholipid chains, as compared to species with unmodified amino termini.
血凝素前体 (HA0) 被细胞蛋白酶切割，形成两个亚单位，HA1 和 HA2。HA2 的 N 端片段，称为融合肽 (HAfp)，具有带电荷的氨基末端。已经表明，HAfp 的 N 端稳定了观察到的 23 个氨基酸长肽 (HAfp1-23) 的螺旋发夹结构，最近已经证明其活性大于 HAfp1-20。在本文中，我们通过与相应的 20-和 23-氨基酸长度的乙酰化肽进行比较，分析 N 端电荷对肽介导融合效率和膜界面构象变化的影响。我们发现，具有未修饰氨基末端的肽具有更高的融合活性，这与其形成垂直于膜平面的螺旋发夹结构的能力相关。分子动力学模拟表明，与具有未修饰氨基末端的肽相比，乙酰化肽更经常采用开放和表面结合的构象，这导致磷脂链的无序度降低。
