Featured Article - January 2011
Short description: The crystal structure of EF-Tu bound to the 70S ribosome solves a 40-year-old puzzle.
For protein synthesis, the ribosome requires additional protein factors, including several GTPases. One such protein is the elongation factor EF-Tu, which takes aminoacyl-tRNA to the ribosome where it forms a complex with GTP, elongation factor G and initiation factor 2.
Hydrolysis of GTP is known to be accompanied by a change in conformation of the switch I and II regions of GTPase. The question that has remained unanswered for nearly 40 years is, how does the ribosome activate GTP hydrolysis?
The crystal structure of EF-Tu bound to the 70S ribosome with Trp-tRNATrp in the presence of the antibiotic paromycin and a GTP analog, solved by Ramakrishnan and colleagues, reveals the active form of EF-Tu.
In this state, the switch I region of the GTPase remains ordered, and no large-scale conformational rearrangements are seen. Instead, the catalytic histidine shifts subtly within the active site to a position where it can act as a general base coordinating the nucleophilic water, ready to attack the γ-phosphate of GTP.
Residue A2662 of the sarcin-ricin loop of the 23S ribosomal RNA is important for the positioning of the active site histidine. This is likely to be a conserved mechanism because all translational GTPases interact with this loop and the catalytic histidine.
R. M. Voorhees et al. The Mechanism for activation of GTP hydrolysis on the ribosome.
Science 330, 835-838 (2010). doi:10.1126/science.1194460