The three lives of viral fusion peptides.
The three lives of viral fusion peptides.
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DOI：
10.1016/j.chemphyslip.2014.03.003
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发表时间：
2014-07
影响因子：
3.4
通讯作者：
Nieva JL
中科院分区：
文献类型：
--
作者：
Apellániz B;Huarte N;Largo E;Nieva JL
融合肽（FP）的存在是病毒融合糖蛋白的标志。FP保守性背后的结构-功能关系仍然非常未知。FP建立满足其在融合前糖蛋白内折叠的相互作用。融合激活后，FP插入并重构靶膜。FP最终可以与跨膜结构域联合收割机结合以形成完整的膜束。融合肽包含来自不同病毒家族的糖蛋白的融合活性绝对需要的保守疏水结构域。经过30年的深入研究，其高度序列保守性的结构和功能尚未完全阐明。长疏水性病毒融合肽（VFP）序列在结构上被限制为在生物合成后进入三个连续状态。首先，VFP序列必须满足糖蛋白复合物的球状胞外域内（Meta）稳定折叠所需的一组天然相互作用。其次，在融合过程开始时，它们被转移到靶细胞膜中并在其中采用特定的构象。根据普遍接受的机制模型，VFP的膜结合状态可能会促进病毒-细胞膜合并所需的脂质双层重塑。最后，至少在某些情况下，几种VFP与跨膜锚定物共组装成膜整体螺旋束，随后假设与融合孔扩张偶联的锁定运动。在这里，我们回顾不同方面的三个主要国家的VFP，包括其他膜转移糖蛋白区域的功能援助，并简要讨论其作为临床干预的目标。
The presence of a fusion peptide (FP) is a hallmark of viral fusion glycoproteins. Structure–function relationships underlying FP conservation remain greatly unknown. FPs establish interactions satisfying their folding within pre-fusion glycoproteins. Upon fusion activation FPs insert into and restructure target membranes. FPs can finally combine with transmembrane domains to form integral membrane bundles. Fusion peptides comprise conserved hydrophobic domains absolutely required for the fusogenic activity of glycoproteins from divergent virus families. After 30 years of intensive research efforts, the structures and functions underlying their high degree of sequence conservation are not fully elucidated. The long-hydrophobic viral fusion peptide (VFP) sequences are structurally constrained to access three successive states after biogenesis. Firstly, the VFP sequence must fulfill the set of native interactions required for (meta) stable folding within the globular ectodomains of glycoprotein complexes. Secondly, at the onset of the fusion process, they get transferred into the target cell membrane and adopt specific conformations therein. According to commonly accepted mechanistic models, membrane-bound states of the VFP might promote the lipid bilayer remodeling required for virus-cell membrane merger. Finally, at least in some instances, several VFPs co-assemble with transmembrane anchors into membrane integral helical bundles, following a locking movement hypothetically coupled to fusion-pore expansion. Here we review different aspects of the three major states of the VFPs, including the functional assistance by other membrane-transferring glycoprotein regions, and discuss briefly their potential as targets for clinical intervention.
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