The Mechanism for Activation of GTP Hydrolysis on the Ribosome

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Science  05 Nov 2010:
Vol. 330, Issue 6005, pp. 835-838
DOI: 10.1126/science.1194460

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A Likely Conformation

At several stages of protein synthesis, guanosine triphosphate hydrolyzing enzymes (GTPases) interact with the ribosome, and GTP hydrolysis is coupled to progression of synthesis. Voorhees et al. (p. 835) have determined a 3.2-resolution structure of the GTPase, elongation factor Tu, which delivers amino-acyl transfer RNA (tRNA) to the ribosome. The GTPase and tRNA were bound to the ribosome and were stalled in an active conformation by a GTP analog. The structure revealed that activation of the enzyme only required small changes in conformation to move a catalytic histidine into the correct position for hydrolysis. A similar mechanism likely applies to the activation of other translational GTPases.


Protein synthesis requires several guanosine triphosphatase (GTPase) factors, including elongation factor Tu (EF-Tu), which delivers aminoacyl–transfer RNAs (tRNAs) to the ribosome. To understand how the ribosome triggers GTP hydrolysis in translational GTPases, we have determined the crystal structure of EF-Tu and aminoacyl-tRNA bound to the ribosome with a GTP analog, to 3.2 angstrom resolution. EF-Tu is in its active conformation, the switch I loop is ordered, and the catalytic histidine is coordinating the nucleophilic water in position for inline attack on the γ-phosphate of GTP. This activated conformation is due to a critical and conserved interaction of the histidine with A2662 of the sarcin-ricin loop of the 23S ribosomal RNA. The structure suggests a universal mechanism for GTPase activation and hydrolysis in translational GTPases on the ribosome.

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