Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate
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- Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate
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Resistance to antibiotics has become a major threat to modern medicine. The ribosome plays a fundamental role in cell vitality by the translation of the genetic code into proteins; hence, it is a major target for clinically useful antibiotics. We report here the cryo-electron microscopy structures of the ribosome of a pathogenic aminoglycoside (AG)-resistant Pseudomonas aeruginosa strain, as well as of a nonresistance strain isolated from a cystic fibrosis patient. The structural studies disclosed defective ribosome complex formation due to a conformational change of rRNA helix H69, an essential intersubunit bridge, and a secondary binding site of the AGs. In addition, a stable conformation of nucleotides A1486 and A1487, pointing into helix h44, is created compared to a non-AG-bound ribosome. We suggest that altering the conformations of ribosomal protein uL6 and rRNA helix H69, which interact with initiation-factor IF2, interferes with proper protein synthesis initiation.
Original language | English |
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Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 116 |
Issue number | 44 |
Pages (from-to) | 22275-22281 |
Number of pages | 7 |
ISSN | 0027-8424 |
DOIs | |
Publication status | Published - 29 Oct 2019 |
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