The crystal structure of human eukaryotic release factor eRF1--mechanism of stop codon recognition and peptidyl-tRNA hydrolysis

Cell. 2000 Feb 4;100(3):311-21. doi: 10.1016/s0092-8674(00)80667-4.


The release factor eRF1 terminates protein biosynthesis by recognizing stop codons at the A site of the ribosome and stimulating peptidyl-tRNA bond hydrolysis at the peptidyl transferase center. The crystal structure of human eRF1 to 2.8 A resolution, combined with mutagenesis analyses of the universal GGQ motif, reveals the molecular mechanism of release factor activity. The overall shape and dimensions of eRF1 resemble a tRNA molecule with domains 1, 2, and 3 of eRF1 corresponding to the anticodon loop, aminoacyl acceptor stem, and T stem of a tRNA molecule, respectively. The position of the essential GGQ motif at an exposed tip of domain 2 suggests that the Gln residue coordinates a water molecule to mediate the hydrolytic activity at the peptidyl transferase center. A conserved groove on domain 1, 80 A from the GGQ motif, is proposed to form the codon recognition site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Codon, Terminator*
  • Crystallography
  • Humans
  • Hydrolysis
  • Models, Molecular
  • Molecular Mimicry
  • Molecular Sequence Data
  • Peptide Chain Termination, Translational*
  • Peptide Termination Factors / chemistry*
  • Peptide Termination Factors / genetics
  • RNA, Transfer / chemistry*
  • RNA, Transfer / metabolism
  • RNA, Transfer, Amino Acyl / chemistry*
  • RNA, Transfer, Amino Acyl / metabolism
  • Recombinant Proteins / chemistry
  • Sequence Homology, Amino Acid


  • Codon, Terminator
  • ETF1 protein, human
  • Peptide Termination Factors
  • RNA, Transfer, Amino Acyl
  • Recombinant Proteins
  • peptide-chain-release factor 3
  • tRNA, peptidyl-
  • RNA, Transfer

Associated data

  • PDB/1DT9