Insights into substrate stabilization from snapshots of the peptidyl transferase center of the intact 70S ribosome

• Published in: Nature structural & molecular biology Vol. 16; no. 5; pp. 528 - 533
• Main Authors: Kelley, Ann C, Voorhees, Rebecca M, Weixlbaumer, Albert, Ramakrishnan, V, Loakes, David
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.05.2009
• Subjects: Biochemistry; Catalysis; Crystallography, X-Ray; Escherichia coli; Molecular biology; Molecular structure; Peptidyl Transferases - metabolism; Physiological aspects; Protein Binding; Protein Structure, Secondary; Protein synthesis; Ribosomal proteins; Ribosomal Proteins - chemistry; Ribosomal Proteins - metabolism; Ribosomes - enzymology; RNA, Ribosomal, 23S - chemistry; RNA, Ribosomal, 23S - metabolism; RNA, Transfer - chemistry; RNA, Transfer - metabolism; Static Electricity; Structure; Substrate Specificity; Thermus thermophilus - metabolism; Transfer RNA; United Kingdom
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/nsmb.1577

Protein synthesis is catalyzed in the peptidyl transferase center (PTC), located in the large (50S) subunit of the ribosome. No high-resolution structure of the intact ribosome has contained a complete active site including both A- and P-site tRNAs. In addition, although past structures of the 50S subunit have found no ordered proteins at the PTC, biochemical evidence suggests that specific proteins are capable of interacting with the 3' ends of tRNA ligands. Here we present structures, at 3.6-A and 3.5-A resolution respectively, of the 70S ribosome in complex with A- and P-site tRNAs that mimic pre- and post-peptidyl-transfer states. These structures demonstrate that the PTC is very similar between the 50S subunit and the intact ribosome. They also reveal interactions between the ribosomal proteins L16 and L27 and the tRNA substrates, helping to elucidate the role of these proteins in peptidyl transfer.