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Virus assembly and maturation: Auto-regulation through allosteric molecular switches

机译:病毒组装和成熟:通过变构分子开关自动调节

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We generalize the concept of allostery from the traditional non-active-site control of enzymes to virus maturation. Virtually, all animal viruses transition from a procapsid noninfectious state to a mature infectious state. The procapsid contains an encoded chemical program that is executed following an environmental cue. We developed an exceptionally accessible virus system for the study of the activators of maturation and the downstream consequences that result in particle stability and infectivity. Nudaurelia capensis omega virus (NωV) is a T = 4 icosahedral virus that undergoes a dramatic maturation in which the 490-? spherical procapsid condenses to a 400-? icosahedral-shaped capsid with associated specific auto-proteolysis and stabilization. Employing X-ray crystallography, time-resolved electron cryo-microscopy and hydrogen/deuterium exchange as well as biochemistry, it was possible to define the mechanisms of allosteric communication among the four quasi-equivalent subunits in the icosahedral asymmetric unit. These gene products undergo proteolysis at different rates, dependent on quaternary structure environment, while particle stability is conferred globally following only a few local subunit transitions. We show that there is a close similarity between the concepts of tensegrity (associated with geodesic domes and mechanical engineering) and allostery (associated with biochemical control mechanisms).
机译:我们将变构的概念从酶的传统非活性部位控制推广到病毒成熟。实际上,所有动物病毒都从无衣壳的非感染状态转变为成熟的感染状态。前衣壳包含根据环境提示执行的编码化学程序。我们开发了一种异常易于访问的病毒系统,用于研究成熟激活因子和导致颗粒稳定性和感染性的下游后果。努德里亚海角茄ω病毒(NωV)是一种T = 4二十面体病毒,经历了戏剧性的成熟,其中490-?球形衣壳凝结成400?二十面体形衣壳,具有相关的特异性自蛋白水解作用和稳定作用。利用X射线晶体学,时间分辨电子冷冻显微镜和氢/氘交换以及生物化学,可以定义二十面体不对称单元中四个准等价亚基之间的变构通讯机理。这些基因产物以不同的速率进行蛋白水解,具体取决于四级结构环境,而仅在少数局部亚基跃迁之后全局赋予颗粒稳定性。我们表明,张力(与测地线穹顶和机械工程相关)和变构(与生化控制机制相关)之间存在密切相似性。

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