Structure of the 70S ribosome bound to release factor 2 and a substrate analog provides insights into catalysis of peptide release.
We report the crystal structure of release factor 2 bound to ribosome with an aminoacyl tRNA substrate analog at the ribosomal P site, at 3.1 A resolution. The structure shows that upon stop-codon recognition, the universally conserved GGQ motif packs tightly into the peptidyl transferase center. Nucleotide A2602 of 23S rRNA, implicated in peptide release, packs with the GGQ motif in release factor 2. The ribose of A76 of the peptidyl-tRNA adopts the C2'-endo conformation, and the 2' hydroxyl of A76 is within hydrogen-bond distance of the 2' hydroxyl of A2451. The structure suggests how a catalytic water can be coordinated in the peptidyl transferase center and, together with previous biochemical and computational data, suggests a model for how the ester bond between the peptidyl tRNA and the nascent peptide is hydrolyzed.
Jin
Hong
H
Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Kelley
Ann C
AC
Loakes
David
D
Ramakrishnan
V
V
D020816:Amino Acid Motifs; D055162:Biocatalysis; D005973:Glutamine / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D009711:Nucleotides / Q000378:metabolism; D010443:Peptide Chain Termination, Translational; D010454:Peptide Termination Factors / Q000737:chemistry* / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010458:Peptidyl Transferases / Q000378:metabolism; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity; D016963:Thermus thermophilus / Q000378:metabolism*; D014867:Water / Q000378:metabolism
D009711:Nucleotides; D010454:Peptide Termination Factors; D010455:Peptides; D012346:RNA, Transfer, Amino Acyl; C041460:peptide chain termination release factor 2; C019037:tRNA, peptidyl-; D014867:Water; D005973:Glutamine; D017665:Hydroxyl Radical; D010458:Peptidyl Transferases