Modulating the activity of the peptidyl transferase center of the ribosome.

The peptidyl transferase (PT) center of the ribosome catalyzes two nucleophilic reactions, peptide bond formation between aminoacylated tRNA substrates and, together with release factor, peptide release. Structure and function of the PT center are modulated by binding of aminoacyl-tRNA or release factor, thus providing the basis for the specificity of catalysis. Another way by which the function of the PT center is controlled is signaling from the peptide exit tunnel. The SecM nascent peptide induces ribosome stalling, presumably by inhibition of peptide bond formation. Similarly, the release factor-induced hydrolytic activity of the PT center can be suppressed by the TnaC nascent peptide contained in the exit tunnel. Thus, local and long-range conformational rearrangements can lead to changes in the reaction specificity and catalytic activity of the PT center.

[1]  T. Martin Schmeing,et al.  An induced-fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-tRNA , 2005, Nature.

[2]  J. S. Weinger,et al.  Substrate-assisted catalysis of peptide bond formation by the ribosome , 2004, Nature Structural &Molecular Biology.

[3]  J. Åqvist,et al.  A model for how ribosomal release factors induce peptidyl-tRNA cleavage in termination of protein synthesis. , 2007, Molecular cell.

[4]  E. Youngman,et al.  The interaction between C75 of tRNA and the A loop of the ribosome stimulates peptidyl transferase activity. , 2006, RNA.

[5]  A. Mankin,et al.  Ribosomal peptidyl transferase can withstand mutations at the putative catalytic nucleotide , 2001, Nature.

[6]  V. Blinov,et al.  Mutations in the highly conserved GGQ motif of class 1 polypeptide release factors abolish ability of human eRF1 to trigger peptidyl-tRNA hydrolysis. , 1999, RNA.

[7]  C. Yanofsky,et al.  Changes produced by bound tryptophan in the ribosome peptidyl transferase center in response to TnaC, a nascent leader peptide. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[8]  H. Noller,et al.  Analysis of mutations at residues A2451 and G2447 of 23S rRNA in the peptidyltransferase active site of the 50S ribosomal subunit , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Malte Beringer,et al.  Essential Mechanisms in the Catalysis of Peptide Bond Formation on the Ribosome* , 2005, Journal of Biological Chemistry.

[10]  Måns Ehrenberg,et al.  Structure of the Escherichia coli ribosomal termination complex with release factor 2 , 2003, Nature.

[11]  A. Mankin,et al.  The critical role of the universally conserved A2602 of 23S ribosomal RNA in the release of the nascent peptide during translation termination. , 2003, Molecular cell.

[12]  Importance of tRNA interactions with 23S rRNA for peptide bond formation on the ribosome: studies with substrate analogs , 2007, Biological chemistry.

[13]  M. Selmer,et al.  Crystal Structures of the Ribosome in Complex with Release Factors RF1 and RF2 Bound to a Cognate Stop Codon , 2005, Cell.

[14]  Thomas A Steitz,et al.  Structural insights into the roles of water and the 2' hydroxyl of the P site tRNA in the peptidyl transferase reaction. , 2005, Molecular cell.

[15]  T. Earnest,et al.  Crystal Structure of the Ribosome at 5.5 Å Resolution , 2001, Science.

[16]  Wolfgang Wintermeyer,et al.  Important contribution to catalysis of peptide bond formation by a single ionizing group within the ribosome. , 2002, Molecular cell.

[17]  E. Youngman,et al.  Stop codon recognition by release factors induces structural rearrangement of the ribosomal decoding center that is productive for peptide release. , 2007, Molecular cell.

[18]  C. Hayes,et al.  Prolyl-tRNAPro in the A-site of SecM-arrested Ribosomes Inhibits the Recruitment of Transfer-messenger RNA* , 2006, Journal of Biological Chemistry.

[19]  A. Geballe,et al.  Coding sequence-dependent ribosomal arrest at termination of translation , 1996, Molecular and cellular biology.

[20]  R. Green,et al.  Two distinct components of release factor function uncovered by nucleophile partitioning analysis. , 2007, Molecular cell.

[21]  S. Strobel,et al.  Exploration of the conserved A+C wobble pair within the ribosomal peptidyl transferase center using affinity purified mutant ribosomes. , 2004, Nucleic acids research.

[22]  C. Yanofsky,et al.  Reproducing tna Operon Regulation in Vitro in an S-30 System , 2001, The Journal of Biological Chemistry.

[23]  Malte Beringer,et al.  Peptide bond formation does not involve acid-base catalysis by ribosomal residues , 2006, Nature Structural &Molecular Biology.

[24]  H. Bernstein,et al.  Translation arrest requires two-way communication between a nascent polypeptide and the ribosome. , 2006, Molecular cell.

[25]  T. Pape,et al.  Complete kinetic mechanism of elongation factor Tu‐dependent binding of aminoacyl‐tRNA to the A site of the E.coli ribosome , 1998, The EMBO journal.

[26]  H. Noller.  Ribosomal RNA and translation. , 1991, Annual review of biochemistry.

[27]  Koreaki Ito,et al.  Genetically encoded but nonpolypeptide prolyl-tRNA functions in the A site for SecM-mediated ribosomal stall. , 2006, Molecular cell.

[28]  J. Frank,et al.  A cryo-electron microscopic study of ribosome-bound termination factor RF2 , 2003, Nature.

[29]  Koreaki Ito,et al.  The Ribosomal Exit Tunnel Functions as a Discriminating Gate , 2002, Cell.

[30]  E. Youngman,et al.  Affinity purification of in vivo-assembled ribosomes for in vitro biochemical analysis. , 2005, Methods.

[31]  S. Dorner,et al.  A conformational change in the ribosomal peptidyl transferase center upon active/inactive transition , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[32]  C. Yanofsky,et al.  Ribosome Recycling Factor and Release Factor 3 Action Promotes TnaC-Peptidyl-tRNA Dropoff and Relieves Ribosome Stalling during Tryptophan Induction of tna Operon Expression in Escherichia coli , 2007, Journal of bacteriology.

[33]  Thomas A Steitz,et al.  Structural insights into peptide bond formation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[34]  C. Yanofsky,et al.  tRNA(Trp) translation of leader peptide codon 12 and other factors that regulate expression of the tryptophanase operon , 1990, Journal of bacteriology.

[35]  D. Barford,et al.  The Crystal Structure of Human Eukaryotic Release Factor eRF1—Mechanism of Stop Codon Recognition and Peptidyl-tRNA Hydrolysis , 2000, Cell.

[36]  M. Rodnina,et al.  The G2447A mutation does not affect ionization of a ribosomal group taking part in peptide bond formation. , 2003, RNA.

[37]  T. Steitz,et al.  The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. , 2000, Science.

[38]  C. Yanofsky,et al.  Instruction of Translating Ribosome by Nascent Peptide , 2002, Science.

[39]  Annette Sievers,et al.  The ribosome as an entropy trap. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[40]  T. Steitz,et al.  The structural basis of ribosome activity in peptide bond synthesis. , 2000, Science.

[41]  J. Åqvist,et al.  Analysis of predictions for the catalytic mechanism of ribosomal peptidyl transfer. , 2006, Biochemistry.

[42]  Malte Beringer,et al.  The ribosomal peptidyl transferase. , 2007, Molecular cell.

[43]  H. Noller,et al.  Unusual resistance of peptidyl transferase to protein extraction procedures. , 1992, Science.

[44]  Jessica A Norman,et al.  Regulation of Escherichia coli secA by Cellular Protein Secretion Proficiency Requires an Intact Gene X Signal Sequence and an Active Translocon , 1998, Journal of bacteriology.

[45]  Jill K Thompson,et al.  The A2453-C2499 wobble base pair in Escherichia coli 23S ribosomal RNA is responsible for pH sensitivity of the peptidyltransferase active site conformation. , 2004, Nucleic acids research.

[46]  M. Ehrenberg,et al.  Regulatory Nascent Peptides in the Ribosomal Tunnel , 2002, Cell.

[47]  J. Åqvist,et al.  Mechanism of peptide bond synthesis on the ribosome. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[48]  S. Dorner,et al.  Molecular aspects of the ribosomal peptidyl transferase. , 2001, Biochemical Society transactions.

[49]  Rachel Green,et al.  The Active Site of the Ribosome Is Composed of Two Layers of Conserved Nucleotides with Distinct Roles in Peptide Bond Formation and Peptide Release , 2004, Cell.

[50]  L. Orgel,et al.  The formation of dipeptides from amino acids and the 2′(3′)-glycyl ester of an adenylate , 1979, Journal of Molecular Evolution.

[51]  R. Brimacombe,et al.  Affinity Purification of Ribosomes with a Lethal G2655C Mutation in 23 S rRNA That Affects the Translocation* , 2003, Journal of Biological Chemistry.

[52]  C. Yanofsky,et al.  Role of leader peptide synthesis in tryptophanase operon expression in Escherichia coli K-12 , 1986, Journal of bacteriology.

[53]  C. Yanofsky,et al.  Features of ribosome-peptidyl-tRNA interactions essential for tryptophan induction of tna operon expression. , 2005, Molecular cell.

[54]  Joachim Frank,et al.  Elongation arrest by SecM via a cascade of ribosomal RNA rearrangements. , 2006, Molecular cell.

[55]  N. Minakawa,et al.  2′/3′‐O‐peptidyl Adenosine as a General Base Catalyst of its Own External Peptidyl Transfer: Implications for the Ribosome Catalytic Mechanism , 2005, Chembiochem : a European journal of chemical biology.

[56]  P. S. Lovett,et al.  Ribosome regulation by the nascent peptide. , 1996, Microbiological reviews.

[57]  C. Yanofsky,et al.  Ribosomal Features Essential for tna Operon Induction: Tryptophan Binding at the Peptidyl Transferase Center , 2007, Journal of bacteriology.

[58]  Frank Schluenzen,et al.  Structural basis of the ribosomal machinery for peptide bond formation, translocation, and nascent chain progression. , 2003, Molecular cell.

[59]  J. Žemlička,et al.  Substrate Specificity of Ribosomal Peptidyl Transferase , 1970 .

[60]  D. P. Burma,et al.  A possible mechanism of peptide bond formation on ribosome without mediation of peptidyl transferase. , 1999, Journal of theoretical biology.