title: Conformational changes of elongation factor G on the ribosome during tRNA translocation.
abstract: The universally conserved GTPase elongation factor G (EF-G) catalyzes the translocation of tRNA and mRNA on the ribosome after peptide bond formation. Despite numerous studies suggesting that EF-G undergoes extensive conformational rearrangements during translocation, high-resolution structures exist for essentially only one conformation of EF-G in complex with the ribosome. Here, we report four atomic-resolution crystal structures of EF-G bound to the ribosome programmed in the pre- and posttranslocational states and to the ribosome trapped by the antibiotic dityromycin. We observe a previously unseen conformation of EF-G in the pretranslocation complex, which is independently captured by dityromycin on the ribosome. Our structures provide insights into the conformational space that EF-G samples on the ribosome and reveal that tRNA translocation on the ribosome is facilitated by a structural transition of EF-G from a compact to an elongated conformation, which can be prevented by the antibiotic dityromycin.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06520-8114, USA.
authors.forename: Matthieu G
authors.initials: MG
authors.lastname: Gagnon
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA; Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA.
authors.forename: David
authors.initials: D
authors.lastname: Bulkley
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA; Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06520-8114, USA. Electronic address: thomas.steitz@yale.edu.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Steitz
mesh_terms: D047630:Depsipeptides / Q000494:pharmacology; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D020653:Peptide Elongation Factor G / Q000737:chemistry* / Q000378:metabolism*; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism*; D016963:Thermus thermophilus / Q000737:chemistry / Q000378:metabolism*; D014961:X-Ray Diffraction
chemical_list: D047630:Depsipeptides; D020653:Peptide Elongation Factor G; D012269:Ribosomal Proteins; C000596509:dityromycin; C049650:ribosomal protein L9; C034212:ribosomal protein S12; D012343:RNA, Transfer