Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, Pawinskiego 5A, 02-106 Warsaw, Poland.
Eur Biophys J. 2011 Mar;40(3):289-303. doi: 10.1007/s00249-010-0647-2. Epub 2010 Dec 9.
Translation on the ribosome is controlled by external factors. During polypeptide lengthening, elongation factors EF-Tu and EF-G consecutively interact with the bacterial ribosome. EF-Tu binds and delivers an aminoacyl-tRNA to the ribosomal A site and EF-G helps translocate the tRNAs between their binding sites after the peptide bond is formed. These processes occur at the expense of GTP. EF-Tu:tRNA and EF-G are of similar shape, share a common binding site, and undergo large conformational changes on interaction with the ribosome. To characterize the internal motion of these two elongation factors, we used 25 ns long all-atom molecular dynamics simulations. We observed enhanced mobility of EF-G domains III, IV, and V and of tRNA in the EF-Tu:tRNA complex. EF-Tu:GDP complex acquired a configuration different from that found in the crystal structure of EF-Tu with a GTP analogue, showing conformational changes in the switch I and II regions. The calculated electrostatic properties of elongation factors showed no global similarity even though matching electrostatic surface patches were found around the domain I that contacts the ribosome, and in the GDP/GTP binding region.
核糖体上的翻译受到外部因素的控制。在多肽延伸过程中,延伸因子 EF-Tu 和 EF-G 相继与细菌核糖体相互作用。EF-Tu 结合并将氨酰基-tRNA 递送到核糖体的 A 位,EF-G 有助于在肽键形成后在 tRNA 结合位点之间进行转移。这些过程以 GTP 的消耗为代价。EF-Tu:tRNA 和 EF-G 形状相似,具有共同的结合位点,并在与核糖体相互作用时发生大的构象变化。为了描述这两个延伸因子的内部运动,我们使用了 25ns 长的全原子分子动力学模拟。我们观察到 EF-G 结构域 III、IV 和 V 以及 EF-Tu:tRNA 复合物中的 tRNA 的迁移率增加。EF-Tu:GDP 复合物获得了与 EF-Tu 与 GTP 类似物的晶体结构中发现的不同构型,在开关 I 和 II 区域显示出构象变化。即使在与核糖体接触的结构域 I 周围以及 GDP/GTP 结合区域发现了匹配的静电表面斑块,计算出的延伸因子的静电性质也没有全局相似性。