David-Eden Hilda, Mandel-Gutfreund Yael
Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Nucleic Acids Res. 2008 Aug;36(14):4641-52. doi: 10.1093/nar/gkn433. Epub 2008 Jul 14.
The ribosome is a complex molecular machine that offers many potential sites for functional interference, therefore representing a major target for antibacterial drugs. The growing number of high-resolution structures of ribosomes from different organisms, in free form and in complex with various ligands, provides unique data for structural and comparative analyses of RNA structures. We model the ribosome structure as a network, where nucleotides are represented as nodes and intermolecular interactions as edges. As shown previously for proteins, we found that the major functional sites of the ribosome exhibit significantly high centrality measures. Specifically, we demonstrate that mutations that strongly affect ribosome function and assembly can be distinguished from mild mutations based on their network properties. Furthermore, we observed that closeness centrality of the rRNA nucleotides is highly conserved in the bacteria, suggesting the network representation as a comparative tool for the ribosome analysis. Finally, we suggest a global topology perspective to characterize functional sites and to reveal the unique properties of the ribosome.
核糖体是一种复杂的分子机器，有许多可能发生功能干扰的位点，因此是抗菌药物的主要作用靶点。来自不同生物体的核糖体的高分辨率结构数量不断增加，这些结构以游离形式以及与各种配体结合的形式存在，为RNA结构的结构分析和比较分析提供了独特的数据。我们将核糖体结构建模为一个网络，其中核苷酸被表示为节点，分子间相互作用被表示为边。正如之前在蛋白质中所显示的那样，我们发现核糖体的主要功能位点表现出显著的高中心性度量。具体而言，我们证明，基于其网络特性，可以将强烈影响核糖体功能和组装的突变与轻度突变区分开来。此外，我们观察到rRNA核苷酸的紧密中心性在细菌中高度保守，这表明网络表示法可作为核糖体分析的比较工具。最后，我们提出了一个全局拓扑视角来表征功能位点并揭示核糖体的独特性质。
