The 30S ribosomal P site: a function of 16S rRNA

Noller, Harry F.; Hoang, Lee; Fredrick, Kurt

doi:10.1016/j.febslet.2004.11.026

Cited by 29 publications

(27 citation statements)

References 27 publications

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“…However, in the 70S complex, peptidyl-tRNA is stabilized at the P site by extensive contacts with the mRNA, 16S RNA and protein residues of the 30S subunit (e.g., Ref. 15), and these interactions are obviously absent in the 50S⦁nc-tRNA complex. On the other hand, the A-site location of the tRNA is stabilized by additional interactions with residues of the 50S subunit that lie outside the peptidyl transfer center (e.g., helix 38 of the 'A-site finger').…”

Section: Discussionmentioning

confidence: 99%

Recycling of Aborted Ribosomal 50S Subunit-Nascent Chain-tRNA Complexes by the Heat Shock Protein Hsp15

Jiang

Schaffitzel

Bingel-Erlenmeyer

et al. 2009

Journal of Molecular Biology

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Section: Discussionmentioning

confidence: 99%

Recycling of Aborted Ribosomal 50S Subunit-Nascent Chain-tRNA Complexes by the Heat Shock Protein Hsp15

Jiang

Schaffitzel

Bingel-Erlenmeyer

et al. 2009

Journal of Molecular Biology

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“…The mimicry suggests that docked CrPV domain 3 can form all the specific intermolecular contacts that occur between the ribosome and an authentic anticodon loopmRNA complex within the decoding center. This is an interesting observation given that the tRNA affinity for the ribosome is highest in the P site 39 , and in bacteria the P site performs a diverse set of functions through very specific contacts with the codon-anticodon structure 40 .…”

Section: Discussionmentioning

confidence: 99%

tRNA–mRNA mimicry drives translation initiation from a viral IRES

Costantino

Pfingsten²,

Rambo

et al. 2007

Nat Struct Mol Biol

142

244

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Internal ribosome entry site (IRES) RNAs initiate protein synthesis in eukaryotic cells by a noncanonical cap-independent mechanism. IRESes are critical for many pathogenic viruses, but efforts to understand their function are complicated by the diversity of IRES sequences as well as by limited high-resolution structural information. The intergenic region (IGR) IRESes of the Dicistroviridae viruses are powerful model systems to begin to understand IRES function. Here we present the crystal structure of a Dicistroviridae IGR IRES domain that interacts with the ribosome's decoding groove. We find that this RNA domain precisely mimics the transfer RNA anticodonmessenger RNA codon interaction, and its modeled orientation on the ribosome helps explain translocation without peptide bond formation. When combined with a previous structure, this work completes the first high-resolution description of an IRES RNA and provides insight into how RNAs can manipulate complex biological machines.Canonical eukaryotic translation initiation is a complex, multistep process in which a modified nucleotide cap on the 5′ end of the mRNA is necessary for protein factor-dependent recruitment of the 40S (small) ribosomal subunit 1 . The subunit scans the message and recognizes the AUG initiation codon, which leads to GTP hydrolysis, initiation factor protein release, and 60S (large) subunit binding to form the 80S ribosome-mRNA complex. The assembled 80S ribosome, containing an initiator tRNA in the P site, begins translation through eukaryotic elongation factor (eEF) 1A-mediated delivery of an aminoacylated tRNA into the A site. Subsequent peptide bond formation in the ribosome's peptidyl transferase site is followed by eEF 2-catalyzed translocation, and the ribosome enters the elongation phase of protein synthesis (Fig. 1a). Thus, canonical cap-dependent translation initiation is driven by the action of many protein factors and begins in the P site from an AUG codon in good context; then translocation occurs after the initial peptide bond is made.In contrast to the canonical cap-dependent pathway, an important alternate mechanism is internal initiation of translation. This mechanism depends on specific cis-acting RNA sequences called IRESes 2,3 . There is great diversity in IRES sequence, secondary structure and requirements for protein factors, but all IRESes recruit, position and activate the proteinmaking machinery without recognizing the cap or the 5′ end of the mRNA. IRESes are critical for the infection of many pathogenic viruses and may be important regulatory elements in gene expression 2 . Insight into the mechanism of many IRESes has been provided by a variety of approaches, but details of their RNA structure-based function remain incomplete. (refs. 4-6 ), and both contact the ribosome over the E site and through the large subunit's L1 stalk 4,5,7,8 . Furthermore, cryo-EM reconstructions of these IRES RNAs bound to the ribosome indicate that both may undergo subtle structural rearrangement during the course of preini...

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“…This mechanism is also applicable to pairs of nonproteinogenic amino acids and amber or other possible elongator tRNAs; particularly, the opposite chirality in D aa is forcefully rejected by this EF-Tu selection filter, resulting in the As the second reason, we suggest that the recognition of initiator D aa-tRNA fMet CAU by P site of ribosome is less strict than that of elongator D aa-tRNAs by the A site. Presumably, since the P site needs to accommodate peptidyltRNA, it has a more spacious pocket than the A site (Noller et al 2005). In fact, our recent studies using various peptidyl-tRNAs for initiation imply that the P site has a surprising tolerance toward the nonproteinogenic peptidyl groups (Y.…”

Section: Discussionmentioning

confidence: 99%

Initiating translation with D-amino acids

Murakami¹,

Suga²

2008

RNA

114

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Here we report experimental evidence that the translation initiation apparatus accepts D-amino acids ( D aa), as opposed to only L-methionine, as initiators. Nineteen D aa, as the stereoisomers to their natural L-amino acids, were charged onto initiator tRNA fMet CAU using flexizyme technology and tested for initiation in a reconstituted Escherichia coli translation system lacking methionine, i.e., the initiator was reprogrammed from methionine to D aa. Remarkably, all D aa could initiate translation while the efficiency of initiation depends upon the type of side chain. The peptide product initiated with D aa was generally in a nonformylated form, indicating that methionyl-tRNA formyltransferase poorly formylated the corresponding

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The 30S ribosomal P site: a function of 16S rRNA

Cited by 29 publications

References 27 publications

Recycling of Aborted Ribosomal 50S Subunit-Nascent Chain-tRNA Complexes by the Heat Shock Protein Hsp15

Recycling of Aborted Ribosomal 50S Subunit-Nascent Chain-tRNA Complexes by the Heat Shock Protein Hsp15

tRNA–mRNA mimicry drives translation initiation from a viral IRES

Initiating translation with D-amino acids

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