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Modulation of lipid polymorphism by the feline leukemia virus fusion peptide: Implications for the fusion mechanism

机译：猫白血病病毒融合肽对脂质多态性的调控：对融合机制的启示

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The structural effects of the fusion peptide of feline leukemia virus (FeLV) on lipid polymorphism were studied, using differential scanning calorimetry (DSC, P-31 nuclear magnetic resonance (NMR), and time-resolved X-ray diffraction. This peptide lowers the bilayer to inverted hexagonal phase transition temperature, T-H, Of dipalmitoleoylphosphatidylethanolamine (DiPoPE) at peptide mole fractions of up to 1.5 x 10(-3) at pH 5.0 and at pH 7.4. The temperature at which isotropic P-31 NMR signals for monomethyldioleoylphosphatidylethanolamine (MeDOPE) first occurred is lowered by the FeLV peptide. The amount of isotropic signal seen at 40 degrees C is directly correlated to the peptide:lipid molar ratio. In the peptide-containing samples, more lipid remains in the isotropic state over the whole recorded temperature range. Isotropic P-31 NMR signals were observed for DiPoPE in the presence of the FeLV peptide for the entire recorded temperature range of 35-50 degrees C, while pure DiPoPE showed no significant amount of isotropic signal. X-ray studies of DiPoPE show the formation of a new lipid phase with peptide, which is not seen in the pure Lipid samples. Disordering of the L-alpha phase is evidenced by broadening of the diffraction peaks, and the hexagonal cell parameter is decreased with peptide present. Our results suggest that the FeLV peptide is increasing the negative curvature of the lipid system, which is thought to be crucial to the formation of highly bent, high-energy structural fusion intermediates, such as the "stalk" model. Fusion activity for this putative fusogenic peptide was also demonstrated, using a resonance energy transfer (RET) Lipid mixing assay. To our knowledge, this work provides the first published experimental evidence of both fusogenic activity and effects on Lipid polymorphism for the FeLV fusion peptide. [References: 47]
机译：用差示扫描量热法（DSC，P-31核磁共振（NMR）和时间分辨X射线衍射）研究了猫白血病病毒（FeLV）融合肽对脂质多态性的结构影响。在pH 5.0和pH 7.4时，肽摩尔分数最高为1.5 x 10（-3）的二棕榈油酰磷脂酰乙醇胺（DiPoPE）的双层至反向六方相变温度TH（DiPoPE）。 FeLV肽降低了首次出现的MeDOPE）。在40摄氏度下观察到的各向同性信号量与肽：脂质摩尔比直接相关。在含肽的样品中，在记录的整个过程中，更多的脂质仍保持各向同性状态在整个记录的温度范围（35-50摄氏度）下，在存在FeLV肽的情况下，在存在FeLV肽的情况下，观察到DiPoPE的各向同性P-31 NMR信号，而纯DiPoPE显示没有明显的各向同性信号。 DiPoPE的X射线研究表明，带有肽的新脂质相形成了，这在纯脂质样品中是看不到的。 L-α相的无序现象通过衍射峰的加宽来证明，并且六角形细胞参数随着存在的肽而降低。我们的结果表明，FeLV肽正在增加脂质系统的负曲率，这被认为对于形成高度弯曲，高能的结构融合中间体（例如“茎”模型）至关重要。还使用共振能量转移（RET）脂质混合测定法证明了该推定融合肽的融合活性。据我们所知，这项工作提供了融合活性和对FeLV融合肽脂质多态性影响的首次公开实验证据。 [参考：47]

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