A cryo-electron microscopic study of ribosome-bound termination factor RF2


Protein synthesis takes place on the ribosome, where genetic information carried by messenger RNA is translated into a sequence of amino acids. This process is terminated when a stop codon moves into the ribosomal decoding centre (DC) and is recognized by a class-1 release factor (RF). RFs have a conserved GGQ amino-acid motif, which is crucial for peptide release and is believed to interact directly with the peptidyl-transferase centre (PTC) of the 50S ribosomal subunit1,2. Another conserved motif of RFs (SPF in RF2) has been proposed to interact directly with stop codons in the DC of the 30S subunit3. The distance between the DC and PTC is 73 Å. However, in the X-ray structure of RF2, SPF and GGQ are only 23 Å apart4, indicating that they cannot be at DC and PTC simultaneously. Here we show that RF2 is in an open conformation when bound to the ribosome, allowing GGQ to reach the PTC while still allowing SPF–stop-codon interaction. The results indicate new interpretations of accuracy in termination, and have implications for how the presence of a stop codon in the DC is signalled to PTC.

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Figure 1: Interaction of RC with RF2.
Figure 2: CPK (Corey–Pauling–Koltun) representation of RF2 domain constellations in the two conformations.
Figure 3: Stereo views showing interaction between functional centres on the RC and RF2 domains.


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We thank M. Kjeldgaard (University of Aarhaus, Denmark) for pre-releasing the RF2 coordinates, T. Tenson (Tarfu University, Estonia) for a critical reading of the manuscript and helpful suggestions, and M. Watters for assistance with the illustrations. This work was supported by the Howard Hughes Medical Institute and by grants from the National Institute of Health (to J.F.) and by the Swedish Foundation for Strategic Research and the Swedish Research Council (to A.V.Z. and M.E.).

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Correspondence to Joachim Frank.

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Rawat, U., Zavialov, A., Sengupta, J. et al. A cryo-electron microscopic study of ribosome-bound termination factor RF2. Nature 421, 87–90 (2003). https://doi.org/10.1038/nature01224

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