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 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.
Song
H
H
Section of Structural Biology, Institute of Cancer Research, London, United Kingdom.
Mugnier
P
P
Das
A K
AK
Webb
H M
HM
Evans
D R
DR
Tuite
M F
MF
Hemmings
B A
BA
Barford
D
D
D000595:Amino Acid Sequence; D018388:Codon, Terminator; D003461:Crystallography; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010443:Peptide Chain Termination, Translational; D010454:Peptide Termination Factors / Q000737:chemistry* / Q000235:genetics; D012343:RNA, Transfer / Q000737:chemistry* / Q000378:metabolism; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
D018388:Codon, Terminator; C489002:ETF1 protein, human; D010454:Peptide Termination Factors; D012346:RNA, Transfer, Amino Acyl; D011994:Recombinant Proteins; C087971:peptide-chain-release factor 3; C019037:tRNA, peptidyl-; D012343:RNA, Transfer