The Crystal Structure of Human Eukaryotic Release Factor eRF1—Mechanism of Stop Codon Recognition and Peptidyl-tRNA Hydrolysis

• Published in: Cell Vol. 100; no. 3; pp. 311 - 321
• Main Authors: Song, Haiwei, Mugnier, Pierre, Das, Amit K, Webb, Helen M, Evans, David R, Tuite, Mick F, Hemmings, Brian A, Barford, David
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.02.2000
• Subjects: 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; Recombinant Proteins - chemistry; release factor eRF1; RNA, Transfer - chemistry; RNA, Transfer - metabolism; RNA, Transfer, Amino Acyl - chemistry; RNA, Transfer, Amino Acyl - metabolism; Sequence Homology, Amino Acid
• ISSN: 0092-8674; 1097-4172
• 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 Å 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 Å from the GGQ motif, is proposed to form the codon recognition site.