Elongation factor 4 remodels the A-site tRNA on the ribosome.

Publication Type:

Journal Article


Proc Natl Acad Sci U S A, Volume 113, Issue 18, p.4994-9 (2016)


Binding Sites, Computer Simulation, Escherichia coli Proteins, Molecular Docking Simulation, Nucleic Acid Conformation, Peptide Initiation Factors, Protein Binding, Protein Conformation, Ribosomes, RNA, Bacterial, RNA, Transfer, RNA-Binding Motifs, RNA-Binding Proteins


<p>During translation, a plethora of protein factors bind to the ribosome and regulate protein synthesis. Many of those factors are guanosine triphosphatases (GTPases), proteins that catalyze the hydrolysis of guanosine 5'-triphosphate (GTP) to promote conformational changes. Despite numerous studies, the function of elongation factor 4 (EF-4/LepA), a highly conserved translational GTPase, has remained elusive. Here, we present the crystal structure at 2.6-Å resolution of the Thermus thermophilus 70S ribosome bound to EF-4 with a nonhydrolyzable GTP analog and A-, P-, and E-site tRNAs. The structure reveals the interactions of EF-4 with the A-site tRNA, including contacts between the C-terminal domain (CTD) of EF-4 and the acceptor helical stem of the tRNA. Remarkably, EF-4 induces a distortion of the A-site tRNA, allowing it to interact simultaneously with EF-4 and the decoding center of the ribosome. The structure provides insights into the tRNA-remodeling function of EF-4 on the ribosome and suggests that the displacement of the CCA-end of the A-site tRNA away from the peptidyl transferase center (PTC) is functionally significant.</p>