In the standard genetic code, there are three mRNA stop codons: UAG ("amber"), UAA ("ochre"), and UGA ("opal" or "umber").
It was discovered by Mario Capecchi in 1967 that, instead, tRNAs do not ordinarily recognize stop codons at all, and that what he named "release factor" was not a tRNA molecule but a protein.
Crystal structures have been solved for bacterial 70S ribosome bound to each of the three release factors, revealing details in codon recognition by RF1/2 and the EF-G-like rotation of RF3.
Fitting the EM images to previously known crystal structures of individual parts provides identification and a more detailed view of the process.
Stop codon recognition activates the RF, promoting a compact to open conformation change,[15] sending the GGQ motif to the peptidyl transferase center (PTC) next to the 3′ end of the P-site tRNA.
By hydrolysis of the peptidyl-tRNA ester bond, which displayed pH-dependence in vitro,[16] the peptide is cut loose and released.
This is done by splitting the ribosome with factors like IF1–IF3 or RRF–EF-G.[17] eRF1 can be broken down into four domains: N-terminal (N), Middle (M), C-terminal (C), plus a minidomain: Unlike in the bacterial version, eRF1–eRF3–GTP binds together into a sub-complex, via a GRFTLRD motif on RF3.
Stop codon recognition makes eRF3 hydrolyze the GTP, and the resulting movement puts the GGQ into the PTC to allow for hydrolysis.