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

The release factor eRF1 terminates protein biosynthesis by recognizing stop codons at the A site of the ribosome and stimulating peptidyl-tRNA bond hy drolysis at the peptidyl transferase center. The crystal structure of human eRF1 to 2.8 Angstrom resolution, combined with mutagenesis analyses of the universal GGQ motif, reveals the molecular mechanism of release factor act ivity. The overall shape and dimensions of eRF1 resemble a tRNA molecule wi th domains 1, 2, and 3 of eRF1 corresponding to the anticodon loop, aminoac yl 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 Gin residue coordinates a water molecule to mediate the hydrolytic activit y at the peptidyl transferase center. A conserved groove on domain 1, 80 An gstrom from the GGQ motif, is proposed to form the codon recognition site.