title: Cryo-EM structure of the mammalian eukaryotic release factor eRF1-eRF3-associated termination complex.
abstract: Eukaryotic translation termination results from the complex functional interplay between two eukaryotic release factors, eRF1 and eRF3, and the ribosome, in which GTP hydrolysis by eRF3 couples codon recognition with peptidyl-tRNA hydrolysis by eRF1. Here, using cryo-electron microscopy (cryo-EM) and flexible fitting, we determined the structure of eRF1-eRF3-guanosine 5'-[β,γ-imido]triphosphate (GMPPNP)-bound ribosomal pretermination complex (pre-TC), which corresponds to the initial, pre-GTP hydrolysis stage of factor attachment. Our results show that eukaryotic translation termination involves a network of interactions between the two release factors and the ribosome. Our structure provides mechanistic insight into the coordination between GTP hydrolysis by eRF3 and subsequent peptide release by eRF1.
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. djt36@case.edu
authors.forename: Derek
authors.initials: D
authors.lastname: Taylor
authors.forename: Anett
authors.initials: A
authors.lastname: Unbehaun
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Sanchaita
authors.initials: S
authors.lastname: Das
authors.forename: Jianlin
authors.initials: J
authors.lastname: Lei
authors.forename: Hstau Y
authors.initials: HY
authors.lastname: Liao
authors.forename: Robert A
authors.initials: RA
authors.lastname: Grassucci
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Pestova
authors.forename: Joachim
authors.initials: J
authors.lastname: Frank
mesh_terms: D000818:Animals; D020285:Cryoelectron Microscopy; D006160:Guanosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D008958:Models, Molecular; D010443:Peptide Chain Termination, Translational; D010454:Peptide Termination Factors / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D011485:Protein Binding; D011487:Protein Conformation; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry / Q000378:metabolism; D011817:Rabbits; D012270:Ribosomes / Q000378:metabolism / Q000648:ultrastructure; D012441:Saccharomyces cerevisiae
chemical_list: C489002:ETF1 protein, human; D010454:Peptide Termination Factors; D012346:RNA, Transfer, Amino Acyl; C087971:peptide-chain-release factor 3; C019037:tRNA, peptidyl-; D006160:Guanosine Triphosphate