Cryo-EM structure of the mammalian eukaryotic release factor eRF1-eRF3-associated termination complex

Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18413-8. doi: 10.1073/pnas.1216730109. Epub 2012 Oct 22.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cryoelectron Microscopy*
  • Guanosine Triphosphate / chemistry
  • Guanosine Triphosphate / metabolism
  • Humans
  • Mammals / metabolism*
  • Models, Molecular
  • Peptide Chain Termination, Translational*
  • Peptide Termination Factors / chemistry
  • Peptide Termination Factors / metabolism
  • Peptide Termination Factors / ultrastructure*
  • Protein Binding
  • Protein Conformation
  • RNA, Transfer, Amino Acyl / chemistry
  • RNA, Transfer, Amino Acyl / metabolism
  • Rabbits
  • Ribosomes / metabolism
  • Ribosomes / ultrastructure
  • Saccharomyces cerevisiae

Substances

  • ETF1 protein, human
  • Peptide Termination Factors
  • RNA, Transfer, Amino Acyl
  • peptide-chain-release factor 3
  • tRNA, peptidyl-
  • Guanosine Triphosphate

Associated data

  • PDB/3J2K