Elongation factor Tu (EF-Tu) is a three-domain protein that is responsible for delivering aminoacyl-tRNA (aa-tRNA) molecules to the ribosome. During the delivery process, EF-Tu undergoes a large-scale (~50Å) conformational transition that results in rearrangement of domain I, relative to the II/III superdomain. Despite the central role of EF-Tu during protein synthesis, little is known about the structural and energetic properties of this reordering process. To study the physical-chemical properties of domain motion, we constructed a multi-basin structure-based (i.e., Gō-like) model, with which we have simulated hundreds of spontaneous conformational rearrangements. By analyzing the statistical properties of these events, we show that EF-Tu is likely to adopt a disordered intermediate ensemble during this transition. We further show that this disordered intermediate will favor a specific sequence of conformational substeps when bound to the ribosome, and the disordered ensemble can influence the kinetics of the incoming aa-tRNA molecule. Overall, this study highlights the dynamic nature of EF-Tu by revealing a relationship between conformational disorder and biological function.
Keywords: conformational change; ribosome; simulation; tRNA selection.
© 2018 Wiley Periodicals, Inc.