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Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate

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 o...

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Autores principales: Halfon, Yehuda, Jimenez-Fernandez, Alicia, La Rosa, Ruggero, Espinosa Portero, Rocio, Krogh Johansen, Helle, Matzov, Donna, Eyal, Zohar, Bashan, Anat, Zimmerman, Ella, Belousoff, Matthew, Molin, Søren, Yonath, Ada
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825255/
https://www.ncbi.nlm.nih.gov/pubmed/31611393
http://dx.doi.org/10.1073/pnas.1909831116
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author Halfon, Yehuda
Jimenez-Fernandez, Alicia
La Rosa, Ruggero
Espinosa Portero, Rocio
Krogh Johansen, Helle
Matzov, Donna
Eyal, Zohar
Bashan, Anat
Zimmerman, Ella
Belousoff, Matthew
Molin, Søren
Yonath, Ada
author_facet Halfon, Yehuda
Jimenez-Fernandez, Alicia
La Rosa, Ruggero
Espinosa Portero, Rocio
Krogh Johansen, Helle
Matzov, Donna
Eyal, Zohar
Bashan, Anat
Zimmerman, Ella
Belousoff, Matthew
Molin, Søren
Yonath, Ada
author_sort Halfon, Yehuda
collection PubMed
description 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.
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spelling pubmed-68252552019-11-06 Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate Halfon, Yehuda Jimenez-Fernandez, Alicia La Rosa, Ruggero Espinosa Portero, Rocio Krogh Johansen, Helle Matzov, Donna Eyal, Zohar Bashan, Anat Zimmerman, Ella Belousoff, Matthew Molin, Søren Yonath, Ada Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2019-10-29 2019-10-14 /pmc/articles/PMC6825255/ /pubmed/31611393 http://dx.doi.org/10.1073/pnas.1909831116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Halfon, Yehuda
Jimenez-Fernandez, Alicia
La Rosa, Ruggero
Espinosa Portero, Rocio
Krogh Johansen, Helle
Matzov, Donna
Eyal, Zohar
Bashan, Anat
Zimmerman, Ella
Belousoff, Matthew
Molin, Søren
Yonath, Ada
Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate
title Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate
title_full Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate
title_fullStr Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate
title_full_unstemmed Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate
title_short Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate
title_sort structure of pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825255/
https://www.ncbi.nlm.nih.gov/pubmed/31611393
http://dx.doi.org/10.1073/pnas.1909831116
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