title: Structural basis for interaction of the ribosome with the switch regions of GTP-bound elongation factors.
abstract: Elongation factor G (EF-G) catalyzes tRNA translocation on the ribosome. Here a cryo-EM reconstruction of the 70S*EF-G ribosomal complex at 7.3 A resolution and the crystal structure of EF-G-2*GTP, an EF-G homolog, at 2.2 A resolution are presented. EF-G-2*GTP is structurally distinct from previous EF-G structures, and in the context of the cryo-EM structure, the conformational changes are associated with ribosome binding and activation of the GTP binding pocket. The P loop and switch II approach A2660-A2662 in helix 95 of the 23S rRNA, indicating an important role for these conserved bases. Furthermore, the ordering of the functionally important switch I and II regions, which interact with the bound GTP, is dependent on interactions with the ribosome in the ratcheted conformation. Therefore, a network of interaction with the ribosome establishes the active GTP conformation of EF-G and thus facilitates GTP hydrolysis and tRNA translocation.
authors.affiliation: Institut für Medizinische Physik und Biophysik, Charite-Universitätsmedizin Berlin, Ziegelstrasse 5-9, 10117 Berlin, Germany.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Connell
authors.forename: Chie
authors.initials: C
authors.lastname: Takemoto
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Wilson
authors.forename: Hongfei
authors.initials: H
authors.lastname: Wang
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Murayama
authors.forename: Takaho
authors.initials: T
authors.lastname: Terada
authors.forename: Mikako
authors.initials: M
authors.lastname: Shirouzu
authors.forename: Maximilian
authors.initials: M
authors.lastname: Rost
authors.forename: Martin
authors.initials: M
authors.lastname: Schüler
authors.forename: Jan
authors.initials: J
authors.lastname: Giesebrecht
authors.forename: Marylena
authors.initials: M
authors.lastname: Dabrowski
authors.forename: Thorsten
authors.initials: T
authors.lastname: Mielke
authors.forename: Paola
authors.initials: P
authors.lastname: Fucini
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Christian M T
authors.initials: CM
authors.lastname: Spahn
mesh_terms: D001665:Binding Sites; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D008958:Models, Molecular; D020653:Peptide Elongation Factor G / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D013329:Structure-Activity Relationship; D016963:Thermus thermophilus / Q000378:metabolism*
chemical_list: D020653:Peptide Elongation Factor G; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate