Dynamic contact network between ribosomal subunits enables rapid large-scale rotation during spontaneous translocation.
Dynamic contact network between ribosomal subunits enables rapid large-scale rotation during spontaneous translocation.
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DOI：
10.1093/nar/gkv649
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发表时间：
2015-08-18
影响因子：
14.9
通讯作者：
Grubmüller H
中科院分区：
文献类型：
--
作者：
Bock LV;Blau C;Vaiana AC;Grubmüller H
在核糖体翻译过程中，两个核糖体亚基通过亚基间桥保持关联，尽管快速大规模的亚基间旋转。没有阻碍轮调的大障碍是快速轮调的先决条件。在这里，我们研究如何实现这样一个平面的自由能景观，特别是考虑到大的转变的桥梁在外围进行。亚基间接触网络的动力学和能量学研究使用分子动力学模拟的原核核糖体在中间状态的自发易位。基于观察到的亚基间接触的发生率，将残基分组为簇。除了中心接触集群，外围集群被发现保持强大的稳定的相互作用，通过改变在旋转过程中的接触。外围B1桥通过改变适应旋转状态的带电残基的接触模式来稳定。相比之下，B4桥的稳定强相互作用由柔性螺旋H34在蛋白质S15的移动之后确保。跨亚基的tRNA对亚基间结合焓的贡献几乎是恒定的，尽管它们在核糖体中的位置不同。这些机制在旋转过程中保持亚基间的相互作用强而稳定，从而防止解离并使快速旋转成为可能。
During ribosomal translation, the two ribosomal subunits remain associated through intersubunit bridges, despite rapid large-scale intersubunit rotation. The absence of large barriers hindering rotation is a prerequisite for rapid rotation. Here, we investigate how such a flat free-energy landscape is achieved, in particular considering the large shifts the bridges undergo at the periphery. The dynamics and energetics of the intersubunit contact network are studied using molecular dynamics simulations of the prokaryotic ribosome in intermediate states of spontaneous translocation. Based on observed occupancies of intersubunit contacts, residues were grouped into clusters. In addition to the central contact clusters, peripheral clusters were found to maintain strong steady interactions by changing contacts in the course of rotation. The peripheral B1 bridges are stabilized by a changing contact pattern of charged residues that adapts to the rotational state. In contrast, steady strong interactions of the B4 bridge are ensured by the flexible helix H34 following the movement of protein S15. The tRNAs which span the subunits contribute to the intersubunit binding enthalpy to an almost constant degree, despite their different positions in the ribosome. These mechanisms keep the intersubunit interaction strong and steady during rotation, thereby preventing dissociation and enabling rapid rotation.