Villa, Elizabeth2; Sengupta, Jayati3; Trabuco, Leonard G.2; Lebarron, J3; Baxter, W. T.3; Shaikh, T. R.3; Grasucci, R. A.3; Nissen, Poul7; Ehrenberg, Måns5; Schulten, Klaus2; Joachim, Frank6
1 Department of Molecular Biology, Faculty of Science, Aarhus University, Aarhus University2 University of Illinois at Urbana-Champaign3 unknown4 Department of Molecular Biology and Genetics - DANDRITE, Department of Molecular Biology and Genetics, Science and Technology, Aarhus University5 Uppsala University6 Columbia University7 Department of Molecular Biology and Genetics - DANDRITE, Department of Molecular Biology and Genetics, Science and Technology, Aarhus University
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-A cryo-electron microscopy map of the aminoacyl-tRNA x EF-Tu x GDP x kirromycin-bound Escherichia 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.
National Academy of Sciences. Proceedings, 2009, Vol 106, Issue 1, p. 1063-1068