Structural dynamics of elongation factor Tu

Abstract

Elongation Factor (EF) Tu is universally conserved and delivers aminoacyl-tRNAs (aatRNAs) to the ribosome. To perform this essential task, EF-Tu binds aa-tRNA in an active GTP-bound state, and GTP hydrolysis is critical for deposition of aa-tRNA into the ribosome. Following each aa-tRNA delivery, nucleotide exchange is required for reactivation of EF-Tu•GDP to EF-Tu•GTP. EF-Tu undergoes a variety of conformational changes during each round of aa-tRNA delivery and reactivation. Here, molecular dynamics simulations in silico and kinetic measurements in vitro demonstrate that structural dynamics of EF-Tu on the sub-nanosecond timescale are correlated with EF-Tu functions on the timescale of seconds. Specifically, structural dynamics of the conserved P-loop and switch II regions are important for nucleotide binding in EF-Tu. Additionally, interactions between domain II of EF-Tu and the small ribosomal subunit, which stimulate GTP hydrolysis on EF-Tu, have the potential to regulate structural dynamics of switch I and switch II.