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Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex
The tripartite multidrug efflux system MexAB-OprM is a major actor in Pseudomonas aeruginosa antibiotic resistance by exporting a large variety of antimicrobial compounds. Crystal structures of MexB and of its Escherichia coli homolog AcrB had revealed asymmetric trimers depicting a directional drug...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532149/ https://www.ncbi.nlm.nih.gov/pubmed/33009415 http://dx.doi.org/10.1038/s41467-020-18770-5 |
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author | Glavier, Marie Puvanendran, Dhenesh Salvador, Dimitri Decossas, Marion Phan, Gilles Garnier, Cyril Frezza, Elisa Cece, Quentin Schoehn, Guy Picard, Martin Taveau, Jean-Christophe Daury, Laetitia Broutin, Isabelle Lambert, Olivier |
author_facet | Glavier, Marie Puvanendran, Dhenesh Salvador, Dimitri Decossas, Marion Phan, Gilles Garnier, Cyril Frezza, Elisa Cece, Quentin Schoehn, Guy Picard, Martin Taveau, Jean-Christophe Daury, Laetitia Broutin, Isabelle Lambert, Olivier |
author_sort | Glavier, Marie |
collection | PubMed |
description | The tripartite multidrug efflux system MexAB-OprM is a major actor in Pseudomonas aeruginosa antibiotic resistance by exporting a large variety of antimicrobial compounds. Crystal structures of MexB and of its Escherichia coli homolog AcrB had revealed asymmetric trimers depicting a directional drug pathway by a conformational interconversion (from Loose and Tight binding pockets to Open gate (LTO) for drug exit). It remains unclear how MexB acquires its LTO form. Here by performing functional and cryo-EM structural investigations of MexB at various stages of the assembly process, we unveil that MexB inserted in lipid membrane is not set for active transport because it displays an inactive LTC form with a Closed exit gate. In the tripartite complex, OprM and MexA form a corset-like platform that converts MexB into the active form. Our findings shed new light on the resistance nodulation cell division (RND) cognate partners which act as allosteric factors eliciting the functional drug extrusion. |
format | Online Article Text |
id | pubmed-7532149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75321492020-10-19 Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex Glavier, Marie Puvanendran, Dhenesh Salvador, Dimitri Decossas, Marion Phan, Gilles Garnier, Cyril Frezza, Elisa Cece, Quentin Schoehn, Guy Picard, Martin Taveau, Jean-Christophe Daury, Laetitia Broutin, Isabelle Lambert, Olivier Nat Commun Article The tripartite multidrug efflux system MexAB-OprM is a major actor in Pseudomonas aeruginosa antibiotic resistance by exporting a large variety of antimicrobial compounds. Crystal structures of MexB and of its Escherichia coli homolog AcrB had revealed asymmetric trimers depicting a directional drug pathway by a conformational interconversion (from Loose and Tight binding pockets to Open gate (LTO) for drug exit). It remains unclear how MexB acquires its LTO form. Here by performing functional and cryo-EM structural investigations of MexB at various stages of the assembly process, we unveil that MexB inserted in lipid membrane is not set for active transport because it displays an inactive LTC form with a Closed exit gate. In the tripartite complex, OprM and MexA form a corset-like platform that converts MexB into the active form. Our findings shed new light on the resistance nodulation cell division (RND) cognate partners which act as allosteric factors eliciting the functional drug extrusion. Nature Publishing Group UK 2020-10-02 /pmc/articles/PMC7532149/ /pubmed/33009415 http://dx.doi.org/10.1038/s41467-020-18770-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Glavier, Marie Puvanendran, Dhenesh Salvador, Dimitri Decossas, Marion Phan, Gilles Garnier, Cyril Frezza, Elisa Cece, Quentin Schoehn, Guy Picard, Martin Taveau, Jean-Christophe Daury, Laetitia Broutin, Isabelle Lambert, Olivier Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex |
title | Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex |
title_full | Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex |
title_fullStr | Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex |
title_full_unstemmed | Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex |
title_short | Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex |
title_sort | antibiotic export by mexb multidrug efflux transporter is allosterically controlled by a mexa-oprm chaperone-like complex |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532149/ https://www.ncbi.nlm.nih.gov/pubmed/33009415 http://dx.doi.org/10.1038/s41467-020-18770-5 |
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