Picky nascent peptides do not talk to foreign ribosomes

Vázquez‐Laslop, Nora; Mankin, Alexander S.

doi:10.1073/pnas.1103011108

Cited by 11 publications

(9 citation statements)

References 21 publications

(27 reference statements)

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“…Binding was about 2-fold stronger with 70S compared to 50S. This in vitro observation with chemically unfolded proteins corroborated with the in vivo data where nascent unfolded (probably partially folded co-translationally) protein was traced to remain associated post-translationally with the 70S that synthesized it and not associated to a free 50S subunit in trans [12, 38]. We argue that this post-translational association of nascent protein to the 70S indeed results into dissociation of that 70S to its subunits.…”

Section: Resultssupporting

confidence: 72%

A Possible Role of the Full-Length Nascent Protein in Post-Translational Ribosome Recycling

et al. 2017

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Each cycle of translation initiation in bacterial cell requires free 50S and 30S ribosomal subunits originating from the post-translational dissociation of 70S ribosome from the previous cycle. Literature shows stable dissociation of 70S from model post-termination complexes by the concerted action of Ribosome Recycling Factor (RRF) and Elongation Factor G (EF-G) that interact with the rRNA bridge B2a/B2b joining 50S to 30S. In such experimental models, the role of full-length nascent protein was never considered seriously. We observed relatively slow release of full-length nascent protein from 50Sof post translation ribosome, and in that process, its toe prints on the rRNA in vivo and in in vitro translation with E.coli S30 extract. We reported earlier that a number of chemically unfolded proteins like bovine carbonic anhydrase (BCA), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), lysozyme, ovalbumin etc., when added to free 70Sin lieu of the full length nascent proteins, also interact with identical RNA regions of the 23S rRNA. Interestingly the rRNA nucleotides that slow down release of the C-terminus of full-length unfolded protein were found in close proximity to the B2a/B2b bridge. It indicated a potentially important chemical reaction conserved throughout the evolution. Here we set out to probe that conserved role of unfolded protein conformation in splitting the free or post-termination 70S. How both the RRF-EFG dependent and the plausible nascent protein–EFG dependent ribosome recycling pathways might be relevant in bacteria is discussed here.

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Section: Resultssupporting

confidence: 72%

A Possible Role of the Full-Length Nascent Protein in Post-Translational Ribosome Recycling

et al. 2017

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“…These observations suggest that these dsCNEs in eukaryotic ribosomes may play a heretofore unknown function for the traffic of nascent polypeptides through the tunnel. The tunnel monitors the structure of the nascent peptide, and specific peptides can signal the ribosome to decrease the rate of elongation or stop translation (Nakatogawa and Ito 2002;Seidelt et al 2009;Cruz-Vera et al 2011;Vázquez-Laslop and Mankin 2011;Wilson and Beckmann 2011;Ito and Chiba 2013). It is conceivable that this signaling mechanism is further elaborated in Eukarya mediated by the eukaryotic-specific dsCNEs that coincide with the tunnel.…”

Section: Domain-specific Cnes (Dscnes)mentioning

confidence: 99%

Universal and domain-specific sequences in 23S–28S ribosomal RNA identified by computational phylogenetics

Doris

Smith

Beamesderfer

et al. 2015

RNA

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Comparative analysis of ribosomal RNA (rRNA) sequences has elucidated phylogenetic relationships. However, this powerful approach has not been fully exploited to address ribosome function. Here we identify stretches of evolutionarily conserved sequences, which correspond with regions of high functional importance. For this, we developed a structurally aligned database, FLORA (full-length organismal rRNA alignment) to identify highly conserved nucleotide elements (CNEs) in 23S-28S rRNA from each phylogenetic domain (Eukarya, Bacteria, and Archaea). Universal CNEs (uCNEs) are conserved in sequence and structural position in all three domains. Those in regions known to be essential for translation validate our approach. Importantly, some uCNEs reside in areas of unknown function, thus identifying novel sequences of likely great importance. In contrast to uCNEs, domain-specific CNEs (dsCNEs) are conserved in just one phylogenetic domain. This is the first report of conserved sequence elements in rRNA that are domain-specific; they are largely a eukaryotic phenomenon. The locations of the eukaryotic dsCNEs within the structure of the ribosome suggest they may function in nascent polypeptide transit through the ribosome tunnel and in tRNA exit from the ribosome. Our findings provide insights and a resource for ribosome function studies.

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“…In the conventional plug scenario, the structure of the tunnel would have little relevance to the mode of macrolide action. However, the ability of the nascent polypeptide to slither through the narrowed crawl space in the drug‐obstructed NPET should be critically influenced by the tunnel architecture, which shows substantial variation between different bacteria 74 (Fig. 8).…”

Section: The Variations In the Npet Structure Affect The Mode Of Actimentioning

confidence: 99%

“…(B) Difference in the shape of the exit tunnels in ribosomes of Gram‐negative ( E. coli , green) and Gram‐positive ( D. radiodurans , orange) bacteria. The figure is reproduced with permission from the reference 74 …”

Section: The Variations In the Npet Structure Affect The Mode Of Actimentioning

confidence: 99%

Macrolide antibiotics in the ribosome exit tunnel: species‐specific binding and action

Kannan

Mankin

2011

Annals of the New York Academy of Sciences

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Macrolide antibiotics bind in the nascent peptide exit tunnel of the ribosome and inhibit protein synthesis. The majority of information on the principles of binding and action of these antibiotics comes from studies that employed model organisms. However, there is a growing understanding that the binding of macrolides to their target, as well as the mode of inhibition of translation, can be strongly influenced by variations in ribosome structure between bacterial species. Awareness of the existence of species-specific differences in drug action and appreciation of the extent of these differences can stimulate future work on developing better macrolide drugs. In this review, representative cases illustrating the organism-specific binding and action of macrolide antibiotics, as well as species-specific mechanisms of resistance are analyzed.

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Picky nascent peptides do not talk to foreign ribosomes

Cited by 11 publications

References 21 publications

A Possible Role of the Full-Length Nascent Protein in Post-Translational Ribosome Recycling

A Possible Role of the Full-Length Nascent Protein in Post-Translational Ribosome Recycling

Universal and domain-specific sequences in 23S–28S ribosomal RNA identified by computational phylogenetics

Macrolide antibiotics in the ribosome exit tunnel: species‐specific binding and action

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