Disorder guides domain rearrangement in elongation factor Tu.
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.
['Yang|Huan|H|', 'Perrier|Jonathan|J|', 'Whitford|Paul C|PC|0000-0001-7104-2265']
D048168:Escherichia coli K12 D029968:Escherichia coli Proteins D064267:Intrinsically Disordered Proteins D008958:Models, Molecular D010444:Peptide Elongation Factor Tu D011485:Protein Binding D011487:Protein Conformation D000072417:Protein Domains D012346:RNA, Transfer, Amino Acyl D012270:Ribosomes D055672:Static Electricity
ribosome simulation conformational change tRNA selection