Elizabeth Villa, Jayati Sengupta, Leonardo G. Trabuco, Jamie LeBarron,
William T. Baxter, Tanvir R. Shaikh, Robert A. Grassucci, Poul Nissen,
Måns Ehrenberg, Klaus Schulten, and Joachim Frank.
Ribosome-induced changes in elongation factor Tu conformation
control GTP hydrolysis.
Proceedings of the National Academy of Sciences, USA,
106:1063-1068, 2009.
VILL2009
In translation, elongation factor Tu (EF-Tu) molecules deliver
aminoacyl-tRNAs to the mRNA-programmed ribosome. The GTPase activity of EF-Tu is triggered by ribosome-induced conformational changes of the factor that play a pivotal role in the selection of the cognate aminoacyl-tRNAs. We present a 6.7-Å cryo-electron microscopy map of the aminoacyl-tRNAEF-TuGDPkirromycin-boundE. coli ribosome, together with an atomic model of the complex obtained
through molecular dynamics flexible fitting. The model reveals the
conformational changes in the conserved GTPase switch regions of EF-Tu
that trigger hydrolysis of GTP, along with key interactions, including
those between the sarcin-ricin loop and the P-loop of EF-Tu, and between the effector loop of EF-Tu and a conserved region of the 16S rRNA. Our data suggest that GTP hydrolysis on EF-Tu is controlled through a hydrophobic gate mechanism.