Eukaryotic protein Release Factor eRF1
Homo sapiens (human)
The synthesis of proteins starts with the traversal of the ribosome across the messenger RNA until it encounters a start codon (a three-letter DNA/RNA sequence). This is followed by a transfer RNA that is complementary to the subsequent codons, attaching amino acids one after another to form a polypeptide chain. This process is terminated when the ribosome encounters a stop codon (three-letter DNA/RNA sequence, usually, UAA, UAG or UGA). This universal process is mediated by protein release factors and GTP and results in the release of a nascent polypeptide chain. Release factors are proteins that bind to the ribosome when it encounters a stop codon and force it to catalyze the addition of a water molecule at the end of the polypeptide chain, thus freeing it from the ribosome. eRF1 is a class 1 release factor which recognizes the stop codon at the A site of the ribosome. It promotes the hydrolysis of the ester bond linking the polypeptide chain with the peptidyl (P) site tRNA, at the peptidyl transfer center of the ribosome.
eRF1 consists of 3 domains, all of which belong to the twisted alpha-beta sandwich class, with a mixed beta sheet core surrounded on both sides by alpha helices. As seen above, the overall shape of eRF1 looks like a Y and resembles a tRNA molecule. Domains 1 and 2 form the two arms of the Y and correspond to the anticodon loop and the aminoacyl acceptor stem of tRNA molecule, respectively. Domain 3 forms the stem of the Y and corresponds to the T stem of tRNA. Domain 2 has the highly conserved GGQ motif at its tip. This motif is necessary for translation termination and the authors propose that a glutamine residue coordinates a water molecule at the peptidyl transferase center of the ribosome, to mediate hydrolytic activity. Domain 1 has a conserved groove with polar and hydrophobic residues, which the authors propose as the site of codon recognition.
Protein Data Bank (PDB)
Song, H. Mugnier, P. Das, A.K. Webb, H.M. Evans, D.R. Tuite, M.F. Hemmings, B.A. Barford, D.; "The crystal structure of human eukaryotic release factor eRF1--mechanism of stop codon recognition and peptidyl-tRNA hydrolysis."; Cell; (2000) 100:311-321 PubMed:10676813.
author: Ashwini Patil