Fulle Simone, Gohlke Holger
Department of Biological Sciences, Molecular Bioinformatics Group, Goethe University, Frankfurt, Germany.
J Mol Biol. 2009 Mar 27;387(2):502-17. doi: 10.1016/j.jmb.2009.01.037. Epub 2009 Jan 27.
A sophisticated interplay between the static properties of the ribosomal exit tunnel and its functional role in cotranslational processes is revealed by constraint counting on topological network representations of large ribosomal subunits from four different organisms. As for the global flexibility characteristics of the subunit, the results demonstrate a conserved stable structural environment of the tunnel. The findings render unlikely that deformations of the tunnel move peptides down the tunnel in an active manner. Furthermore, the stable environment rules out that the tunnel can adapt widely so as to allow tertiary folding of nascent chains. Nevertheless, there are local zones of flexible nucleotides within the tunnel, between the peptidyl transferase center and the tunnel constriction, and at the tunnel exit. These flexible zones strikingly agree with previously identified folding zones. As for cotranslational elongation regulation, flexible residues in the beta-hairpin of the ribosomal L22 protein were verified, as suggested previously based on structural results. These results support the hypothesis that L22 can undergo conformational changes that regulate the tunnel voyage of nascent polypeptides. Furthermore, rRNA elements, for which conformational changes have been observed upon interaction of the tunnel wall with a nascent SecM peptide, are less strongly coupled to the subunit core. Sequences of coupled rigid clusters are identified between the tunnel and some of these elements, suggesting signal transmission by a domino-like mechanical coupling. Finally, differences in the flexibility of the glycosidic bonds of bases that form antibiotics-binding crevices within the peptidyl transferase center and the tunnel region are revealed for ribosomal structures from different kingdoms. In order to explain antibiotics selectivity, action, and resistance, according to these results, differences in the degrees of freedom of the binding regions may need to be considered.
通过对来自四种不同生物体的大核糖体亚基的拓扑网络表示进行约束计数，揭示了核糖体出口通道的静态特性与其在共翻译过程中的功能作用之间的复杂相互作用。至于亚基的全局灵活性特征，结果表明通道具有保守的稳定结构环境。这些发现使得通道变形以主动方式将肽沿着通道向下移动的可能性不大。此外，稳定的环境排除了通道能够广泛适应以允许新生链进行三级折叠的可能性。然而，在通道内、肽基转移酶中心和通道收缩之间以及通道出口处存在柔性核苷酸的局部区域。这些柔性区域与先前确定的折叠区域惊人地一致。至于共翻译延伸调控，核糖体L22蛋白β发夹中的柔性残基得到了验证，正如先前基于结构结果所暗示的那样。这些结果支持了L22可以发生构象变化来调节新生多肽通道行程的假设。此外，在通道壁与新生的SecM肽相互作用时观察到构象变化的rRNA元件与亚基核心的耦合较弱。在通道与其中一些元件之间鉴定出了耦合刚性簇的序列，表明通过多米诺骨牌样机械耦合进行信号传递。最后，揭示了来自不同界的核糖体结构在肽基转移酶中心和通道区域内形成抗生素结合裂隙的碱基糖苷键灵活性的差异。为了解释抗生素的选择性、作用和抗性，根据这些结果，可能需要考虑结合区域自由度的差异。
