The Structure of the Ribosome with Elongation Factor G Trapped in the Posttranslocational State

Ribosomes Caught in Translation To synthesize proteins, the ribosome must select cognate transfer RNAs (tRNAs) based on base-pairing with the messenger RNA (mRNA) template (a process known as decoding), form a peptide bond, and then move the mRNA:tRNA assembly relative to the ribosome (a process known as translocation). Decoding and translocation require protein guanosine triphosphatases (GTPases), and, while high-resolution structures of the ribosome have greatly furthered our understanding of ribosome function, the detailed mechanism of these GTPases during the elongation cycle remains unclear. Two Research Articles now give a clearer view of these steps in bacterial protein synthesis (see the Perspective by Liljas). Schmeing et al. (p. 688, published online 15 October) present the crystal structure of the ribosome bound to Elongation factor-Tu (EF-Tu) and amino-acyl tRNA that gives insight into how EF-Tu contributes to accurate decoding. Gao et al. (p. 694, published online 15 October) describe the crystal structure of the ribosome bound to Elongation factor-G (EF-G) trapped in a posttranslocation state by the antibiotic fusidic acid that gives insight into how EF-G functions in translocation. Crystal structures of the ribosome bound to elongation factors provide insights into translocation and decoding. Elongation factor G (EF-G) is a guanosine triphosphatase (GTPase) that plays a crucial role in the translocation of transfer RNAs (tRNAs) and messenger RNA (mRNA) during translation by the ribosome. We report a crystal structure refined to 3.6 angstrom resolution of the ribosome trapped with EF-G in the posttranslocational state using the antibiotic fusidic acid. Fusidic acid traps EF-G in a conformation intermediate between the guanosine triphosphate and guanosine diphosphate forms. The interaction of EF-G with ribosomal elements implicated in stimulating catalysis, such as the L10-L12 stalk and the L11 region, and of domain IV of EF-G with the tRNA at the peptidyl-tRNA binding site (P site) and with mRNA shed light on the role of these elements in EF-G function. The stabilization of the mobile stalks of the ribosome also results in a more complete description of its structure.

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