Abstract
Aminoglycosides are widely used antibiotics that cause messenger RNA decoding errors, block mRNA and transfer RNA translocation, and inhibit ribosome recycling. Ribosome recycling follows the termination of protein synthesis and is aided by ribosome recycling factor (RRF) in bacteria. The molecular mechanism by which aminoglycosides inhibit ribosome recycling is unknown. Here we show in X-ray crystal structures of the Escherichia coli 70S ribosome that RRF binding causes RNA helix H69 of the large ribosomal subunit, which is crucial for subunit association, to swing away from the subunit interface. Aminoglycosides bind to H69 and completely restore the contacts between ribosomal subunits that are disrupted by RRF. These results provide a structural explanation for aminoglycoside inhibition of ribosome recycling.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Aminoglycosides / chemistry*
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Aminoglycosides / pharmacology
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology
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Binding Sites
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Crystallography, X-Ray
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Escherichia coli / drug effects*
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Escherichia coli / genetics
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Gentamicins / chemistry
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Gentamicins / pharmacology
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Models, Molecular
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Molecular Structure
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Neomycin / chemistry
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Neomycin / pharmacology
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Paromomycin / chemistry
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Paromomycin / pharmacology
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Protein Subunits / chemistry
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Ribosomal Proteins / chemistry*
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Ribosomes / chemistry*
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Structure-Activity Relationship
Substances
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Aminoglycosides
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Anti-Bacterial Agents
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Gentamicins
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Protein Subunits
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Ribosomal Proteins
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ribosome releasing factor
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Paromomycin
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Neomycin
Associated data
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PDB/2QAL
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PDB/2QAM
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PDB/2QAN
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PDB/2QAO
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PDB/2QB9
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PDB/2QBA
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PDB/2QBB
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PDB/2QBC
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PDB/2QBD
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PDB/2QBE
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PDB/2QBF
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PDB/2QBG
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PDB/2QBH
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PDB/2QBI
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PDB/2QBJ
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PDB/2QBK
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PDB/2Z4K
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PDB/2Z4L
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PDB/2Z4M
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PDB/2Z4N