Structural basis for aminoglycoside inhibition of bacterial ribosome recycling

Borovinskaya, M.A.; Pai, R.D.; Zhang, Wen; Schuwirth, B.S.; Holton, James M.; Hirokawa, Go; Kaji, Hideko; Kaji, Akira; Cate, J.H.D.

doi:10.1038/nsmb1271

Cited by 337 publications

(399 citation statements)

References 45 publications

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“…Co‐crystal structures of a variety of bound aminoglycosides have been published, including with streptomycin ( 31 , PDB ID: 1FJG),110 spectinomycin ( 32 , PDB ID: 1FJG),110 hygromycin B ( 33 , PDB ID: 1HNZ),97 neomycin B ( 34 , PDB ID: 4V52),111 paromomycin ( 35 , PDB ID: 1FJG, 1IBK),110, 112 tobramycin ( 36 , PDB ID: 1LC4),113 and kanamycin A ( 37 , PDB ID: 2ESI) 109…”

Section: Protein Synthesis Inhibitorsmentioning

confidence: 99%

Targeting Antibiotic Resistance

2016

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Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human‐pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last‐resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens.

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Section: Protein Synthesis Inhibitorsmentioning

confidence: 99%

Targeting Antibiotic Resistance

2016

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“…2A). The altered ribosomal distribution in the presence of gentamicin could be caused by cellfixation artifacts (33), gentamicin-induced cellular stress (34,35), a reduction in the ribosome recycling rate (36), or an increase in the ratio of monosomes to polysomes (37).…”

Section: Use Of Immunoelectron Microscopy and An Antibody-independentmentioning

confidence: 99%

Spatially segregated transcription and translation in cells of the endomembrane-containing bacterium Gemmata obscuriglobus

Gottshall

Seebart

Gatlin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The dogma of coupled transcription and translation in bacteria has been challenged by recent reports of spatial segregation of these processes within the relatively simple cellular organization of the model organisms Escherichia coli and Bacillus subtilis. The bacterial species Gemmata obscuriglobus possesses an extensive endomembrane system. The membranes generate a very convoluted intracellular architecture in which some of the cell's ribosomes appear to have less direct access to the cell's nucleoid(s) than others. This observation prompted us to test the hypothesis that a substantial proportion of G. obscuriglobus translation may be spatially segregated from transcription. Using immunofluorescence and immunoelectron microscopy, we showed that translating ribosomes are localized throughout the cell, with a quantitatively greater proportion found in regions distal to nucleoid(s). Our results extend information about the phylogenetic and morphological diversity of bacteria in which the spatial organization of transcription and translation has been studied. These findings also suggest that endomembranes may provide an obstacle to colocated transcription and translation, a role for endomembranes that has not been reported previously for a prokaryotic organism. Our studies of G. obscuriglobus may provide a useful background for consideration of the evolutionary development of eukaryotic cellular complexity and how it led to decoupled processes of gene expression in eukaryotes.

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“…We examined whether codons (or anticodons) assigned to each amino acid by the canonical genetic code were enriched near the respective amino acid in the ribosome. Structures of ribosomes from four species (one archaebacterium and three eubacteria) (14)(15)(16)(17) were analyzed. Many amino acids were found to contact their codon (or anticodon) sequences in rRNAs (Fig.…”

Section: Codons or Anticodons For Select Amino Acids Are Enriched Neamentioning

confidence: 99%

Imprints of the genetic code in the ribosome

Johnson

Wang

2010

Proc. Natl. Acad. Sci. U.S.A.

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The establishment of the genetic code remains elusive nearly five decades after the code was elucidated. The stereochemical hypothesis postulates that the code developed from interactions between nucleotides and amino acids, yet supporting evidence in a biological context is lacking. We show here that anticodons are selectively enriched near their respective amino acids in the ribosome, and that such enrichment is significantly correlated with the canonical code over random codes. Ribosomal anticodon-amino acid enrichment further reveals that specific codons were reassigned during code evolution, and that the code evolved through a two-stage transition from ancient amino acids without anticodon interaction to newer additions with anticodon interaction. The ribosome thus serves as a molecular fossil, preserving biological evidence that anticodonamino acid interactions shaped the evolution of the genetic code.evolution of the genetic code | stereochemical hypothesis | anticodonamino acid association | codon reassignment | RNA-protein interaction T he origin and evolution of the genetic code is a critical transition in the evolution of all modern organisms (1). Understanding why the genetic code evolved to its modern form is as important, if not more so, as knowing the code itself (2), as it is central to understanding major evolutionary breakthroughs. However, the universality of the code is also its downfall with regard to studying its formation, as no organisms exist containing a primitive or intermediate genetic code for comparison. Although multiple hypotheses have been proposed to explain why codons are selectively assigned to specific amino acids (3, 4), empirical data are extremely rare and difficult to obtain (5-8), leaving many theories in the realm of conjecture. One theory addressing this challenging question is the stereochemical hypothesis, which postulates that the genetic code developed from interactions between anticodon-or codon-containing polynucleotides and their respective amino acids (5, 9). This theory is supported by RNA aptamer experiments, in which RNA molecules evolved to bind specific amino acids in vitro are enriched with anticodon and codon elements for the amino acid (6-8, 10). Codons for arginine have also been found to confer binding specificity for arginine in the self-splicing group I introns (11). Nonetheless, the biological relevance of these aptamers and introns to genetic code evolution is unknown, and no further in vivo data exist to support this hypothesis.If chemical or physical interactions between nucleotides and amino acids did influence the evolution of the genetic code, relics of this evolution may be present in modern cells. In particular, we may uncover such imprints within RNA-binding proteins and RNAprotein interactions. The ribosome presents an excellent model for the study of these potential interactions, as it is a large ribonucleoprotein complex with some 50 proteins interacting extensively with the ribosomal RNAs (rRNAs) for stability and structure (Fig. 1A) (...

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Structural basis for aminoglycoside inhibition of bacterial ribosome recycling

Cited by 337 publications

References 45 publications

Targeting Antibiotic Resistance

Targeting Antibiotic Resistance

Spatially segregated transcription and translation in cells of the endomembrane-containing bacterium Gemmata obscuriglobus

Imprints of the genetic code in the ribosome

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