Department of Chemistry, 418 Seeley G Mudd Building, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089-1062, USA.
Proc Natl Acad Sci U S A. 2011 Jun 14;108(24):9827-32. doi: 10.1073/pnas.1105714108. Epub 2011 May 26.
The crucial process of aminoacyl-tRNA delivery to the ribosome is energized by the GTPase reaction of the elongation factor Tu (EF-Tu). Advances in the elucidation of the structure of the EF-Tu/ribosome complex provide the rare opportunity of gaining a detailed understanding of the activation process of this system. Here, we use quantitative simulation approaches and reproduce the energetics of the GTPase reaction of EF-Tu with and without the ribosome and with several key mutants. Our study provides a novel insight into the activation process. It is found that the critical H84 residue is not likely to behave as a general base but rather contributes to an allosteric effect, which includes a major transition state stabilization by the electrostatic effect of the P loop and other regions of the protein. Our findings have general relevance to GTPase activation, including the processes that control signal transduction.
氨酰基-tRNA 向核糖体的输送是由延伸因子 Tu（EF-Tu）的 GTP 酶反应提供能量的。EF-Tu/核糖体复合物结构的阐明进展为深入了解该系统的激活过程提供了难得的机会。在这里，我们使用定量模拟方法，复制了 EF-Tu 与核糖体结合和不结合以及几个关键突变体的 GTP 酶反应的能量学。我们的研究为激活过程提供了新的见解。研究发现，关键的 H84 残基不太可能作为一个普遍的碱基，而是有助于变构效应，其中包括 P 环和蛋白质的其他区域的静电效应对主要过渡态的稳定作用。我们的发现对 GTP 酶激活具有普遍意义，包括控制信号转导的过程。
