Crystal structures of the ribosome in complex with release factors RF1 and RF2 bound to a cognate stop codon.
During protein synthesis, translational release factors catalyze the release of the polypeptide chain when a stop codon on the mRNA reaches the A site of the ribosome. The detailed mechanism of this process is currently unknown. We present here the crystal structures of the ribosome from Thermus thermophilus with RF1 and RF2 bound to their cognate stop codons, at resolutions of 5.9 Angstrom and 6.7 Angstrom, respectively. The structures reveal details of interactions of the factors with the ribosome and mRNA, including elements previously implicated in decoding and peptide release. They also shed light on conformational changes both in the factors and in the ribosome during termination. Differences seen in the interaction of RF1 and RF2 with the L11 region of the ribosome allow us to rationalize previous biochemical data. Finally, this work demonstrates the feasibility of crystallizing ribosomes with bound factors at a defined state along the translational pathway.
Petry
Sabine
S
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom.
Brodersen
Ditlev E
DE
Murphy
Frank V
FV
Dunham
Christine M
CM
Selmer
Maria
M
Tarry
Michael J
MJ
Kelley
Ann C
AC
Ramakrishnan
V
V
D000595:Amino Acid Sequence; D018388:Codon, Terminator / Q000737:chemistry*; D018360:Crystallography, X-Ray / Q000379:methods / Q000706:statistics & numerical data; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010454:Peptide Termination Factors / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D016963:Thermus thermophilus
D018388:Codon, Terminator; D010454:Peptide Termination Factors; D010455:Peptides; C041460:peptide chain termination release factor 2