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首页> 外文期刊>Physical Review X >Long-Range Cooperative Disassembly and Aging During Adenovirus Uncoating
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Long-Range Cooperative Disassembly and Aging During Adenovirus Uncoating

机译:在腺病毒的远程合作拆卸和老化

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Icosahedral virus capsids are closed shells built up with a hexagonal lattice of proteins, which incorporate pentamers at their fivefold vertices. Human adenovirus particles lose pentamers (pentons) during infection under a variety of physicochemical cues, including mechanical pulling of molecular motors and the viscous drag of the cytoplasm. By combining atomic force microscopy experiments with survival analysis and Markovian transition state theory, we investigate the sequence of adenovirus penton disassembly that reveals the aging of the virus structure. We show evidence that the lifetime of pentons gradually decreases, accompanied by capsid softening as neighboring pentons are lost. This cooperative dismantling process, which involves first-neighbor penton-penton distances of at least 45?nm, leads to a 50% increase in the virus disassembling rate of the virus particle. Theory and experiments fit remarkably well, allowing us to obtain the spontaneous escape rate and the energy barrier of penton disassembly ( ~ 30 k B T ). The observed increase in the penton’s loss rate reveals long-range structural correlations within the capsid. Our estimations suggest that the mechanical cues arising from the strokes of protein motors carrying the virus to the nucleus could help penton disassembly and warrant the timely delivery of weak-enough capsids for adenovirus infection.
机译:ICOSAHEDRAL病毒衣壳封闭壳体封闭壳,含有六边形蛋白质的蛋白质,它在其五倍顶点掺入五碎片。人腺病毒颗粒在各种物理化学提示下感染期间失去五聚体(柱子),包括机械拉动分子电机和细胞质的粘性阻力。通过将原子力显微镜实验与生存分析和马尔科夫过渡状态理论相结合,研究了揭示病毒结构老化的腺病毒柱脱索序列。我们展示了证据表明,由于邻近的柱子丢失,伴随着糖零的寿命逐渐降低。这种合作拆除过程,涉及至少45μm的第一邻柱 - 柱距离,导致病毒颗粒的病毒拆卸率增加50%。理论和实验非常好,允许我们获得自发的逃脱率和柱子拆卸的能量屏障(〜30kb t)。观察到的枢零损失率的增加显示了衣壳内的远程结构相关性。我们的估计表明,从核心携带病毒的蛋白质电机冲程引起的机械提示可以帮助柱子拆卸,并保证及时交付足够弱足够的腺瘤感染。

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