Modulating the activity of the peptidyl transferase center of the ribosome

Beringer, Malte

doi:10.1261/rna.980308

Cited by 25 publications

(23 citation statements)

References 62 publications

(84 reference statements)

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“…In the PTC there is just 1 nt difference: U3780C. But even a single difference in such a conserved region is worth noticing, knowing that in the prokaryote PTC-equivalent, individual nucleotides have specific roles in the translation process and some mutations result in a lethal phenotype (Beringer 2008;Polacek and Mankin 2008;Long et al 2009Long et al , 2010Yang et al 2009;Chirkova et al 2010).…”

Section: Structural and Functional Implications Of The Lsu Rrna Typesmentioning

confidence: 99%

Expression of distinct maternal and somatic 5.8S, 18S, and 28S rRNA types during zebrafish development

Locati

Pagano

Girard

et al. 2017

RNA

127

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There is mounting evidence that the ribosome is not a static translation machinery, but a cell-specific, adaptive system. Ribosomal variations have mostly been studied at the protein level, even though the essential transcriptional functions are primarily performed by rRNAs. At the RNA level, oocyte-specific 5S rRNAs are long known for Xenopus. Recently, we described for zebrafish a similar system in which the sole maternal-type 5S rRNA present in eggs is replaced completely during embryonic development by a somatic-type. Here, we report the discovery of an analogous system for the 45S rDNA elements: 5.8S, 18S, and 28S. The maternal-type 5.8S, 18S, and 28S rRNA sequences differ substantially from those of the somatic-type, plus the maternal-type rRNAs are also replaced by the somatic-type rRNAs during embryogenesis. We discuss the structural and functional implications of the observed sequence differences with respect to the translational functions of the 5.8S, 18S, and 28S rRNA elements. Finally, in silico evidence suggests that expansion segments (ES) in 18S rRNA, previously implicated in ribosome-mRNA interaction, may have a preference for interacting with specific mRNA genes. Taken together, our findings indicate that two distinct types of ribosomes exist in zebrafish during development, each likely conducting the translation machinery in a unique way.

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Section: Structural and Functional Implications Of The Lsu Rrna Typesmentioning

confidence: 99%

Expression of distinct maternal and somatic 5.8S, 18S, and 28S rRNA types during zebrafish development

Locati

Pagano

Girard

et al. 2017

RNA

127

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“…In fact, certain nascent peptides were shown to affect the activity of the peptidyltransferase center, indicating specific interactions between the nascent peptide and residues of the ribosome tunnel that are signaled to the catalytic center (reviewed in Ref. 42).…”

Section: Modulation Of Reaction Rates By the Nature Of The P-sitementioning

confidence: 99%

“…The presence of Pro-tRNA Pro in the peptidyltransferase center may predispose the ribosome to stall upon synthesis of SecM (68). Such a model would imply that a slow reaction involving ProtRNA Pro gives the signal coming from the peptide tunnel sufficient time to trigger further conformational changes in the active site that lead to complete inhibition of the reaction (42).…”

mentioning

confidence: 99%

Modulation of the Rate of Peptidyl Transfer on the Ribosome by the Nature of Substrates

Wohlgemuth

Brenner

Beringer

et al. 2008

Journal of Biological Chemistry

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152

194

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The ribosome catalyzes peptide bond formation between peptidyl-tRNA in the P site and aminoacyl-tRNA in the A site. Here, we show that the nature of the C-terminal amino acid residue in the P-site peptidyl-tRNA strongly affects the rate of peptidyl transfer. Depending on the C-terminal amino acid of the peptidyl-tRNA, the rate of reaction with the small A-site substrate puromycin varied between 100 and 0.14 s ؊1 , regardless of the tRNA identity. The reactivity decreased in the order Lys ‫؍‬ Arg > Ala > Ser > Phe ‫؍‬ Val > Asp Ͼ Ͼ Pro, with Pro being by far the slowest. However, when Phe-tRNA Phe was used as A-site substrate, the rate of peptide bond formation with any peptidyl-tRNA was ϳ7 s ؊1 , which corresponds to the rate of binding of Phe-tRNA Phe to the A site (accommodation). Because accommodation is rate-limiting for peptide bond formation, the reaction rate is uniform for all peptidyltRNAs, regardless of the variations of the intrinsic chemical reactivities. On the other hand, the 50-fold increase in the reaction rate for peptidyl-tRNA ending with Pro suggests that full-length aminoacyl-tRNA in the A site greatly accelerates peptide bond formation.The enzymatic activity of the ribosome is to catalyze peptide bond formation. During the peptidyl transfer reaction, the ␣-amino group of aminoacyl-tRNA bound to the A site of the ribosome attacks the ester bond of peptidyl-tRNA in the P site, which results in peptidyl-tRNA extended by one amino acid in the A site and deacylated tRNA in the P site. The tRNA substrates are aligned in the active center of the ribosome by interactions of their CCA ends with 23 S rRNA bases (1-3). The ribosome lowers the activation entropy of the reaction (4, 5) by orienting the reacting groups precisely relative to each other (2, 3), providing an electrostatic environment that reduces the free energy of forming the transition state, shielding the reaction against bulk water (6, 7), or a combination of these effects (8).The peptidyl transfer reaction is modulated by conformational changes at the active site (3, 8 -10) as well as by the nature of the substrates. Rapid peptide bond formation requires fulllength tRNA in both A and P sites, and the reaction rate is influenced by the length of the tRNA fragments when model substrates are used (8, 10 -14). The reaction rate is also influenced by the nature of the amino acid side chain of the A-site substrate (13,(15)(16)(17), but is independent of the nucleophilicity of the attacking amino group in model substrates (18). Moreover, the length of the peptidyl chain and the nature of the C-terminal amino acid of the peptidyl-tRNA in the P site seem to have an effect (10,12,13,19). Early studies with 50 S ribosomal subunits indicated that efficient peptidyl transfer was observed with 3Ј-terminal RNase T1 fragments of N-acetylArg-tRNA Arg and fMet-tRNA fMet as model P-site substrates and an analog of aminoacyl-tRNA, puromycin (Pmn 4 ; O-methyltyrosine linked to N 6 -dimethyladenosine via an amide bond), as A-site substrate (20). In contrast,...

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“…The exit tunnel accommodates at least 30 residues of nascent polypeptide in alpha-helical conformation (34,42,46). The SecM polypeptide undergoes a regulatory translation arrest at residue Pro-166, in which the essential residue Trp-155 lies near a constriction in the exit tunnel formed by protrusions of proteins L4 and L22 and domain II of 16S rRNA (1,34,37).…”

mentioning

confidence: 99%

“…Here, it has illuminated our understanding of ribosome structure, function, and regulation. The single-minded pursuit of mechanism for tnaAB control has generated an experimental and conceptual model for nascent peptide control in other contexts (1,12,33,34,37).…”

mentioning

confidence: 99%

The Ribosome: a Metabolite-Responsive Transcription Regulator

Stewart

2008

J Bacteriol

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Modulating the activity of the peptidyl transferase center of the ribosome

Cited by 25 publications

References 62 publications

Expression of distinct maternal and somatic 5.8S, 18S, and 28S rRNA types during zebrafish development

Expression of distinct maternal and somatic 5.8S, 18S, and 28S rRNA types during zebrafish development

Modulation of the Rate of Peptidyl Transfer on the Ribosome by the Nature of Substrates

The Ribosome: a Metabolite-Responsive Transcription Regulator

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