Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex
| Autor: | Isabelle Broutin, Dimitri Salvador, Marion Decossas, Gilles Phan, Martin Picard, Dhenesh Puvanendran, Jean-Christophe Taveau, Guy Schoehn, Marie Glavier, Quentin Cece, Cyril Garnier, Olivier Lambert, Laetitia Daury, Elisa Frezza |
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| Přispěvatelé: | Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), ANR-17-CE11-0028,MISTEC,Systèmes d'efflux minimaux pour l'étude fonctionnelle des complexes tripartites de la paroi bactérienne(2017), ANR-16-CE11-0001,inVIVE,Bases moléculaires du transport actif d'antibiotiques par la pompe d'efflux MexA-MexB-OprM de Pseudomonas aeruginosa. in vitro veritas(2016) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Science [SDV]Life Sciences [q-bio] Protein domain Allosteric regulation General Physics and Astronomy Antimicrobial resistance medicine.disease_cause Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Allosteric Regulation Protein Domains Cryoelectron microscopy Membrane proteins medicine lcsh:Science Escherichia coli 030304 developmental biology 0303 health sciences Multidisciplinary biology Pseudomonas aeruginosa Chemistry Drug Pathway Biological Transport Transporter General Chemistry biochemical phenomena metabolism and nutrition Anti-Bacterial Agents 3. Good health Cell biology Chaperone (protein) biology.protein lcsh:Q Efflux 030217 neurology & neurosurgery Bacterial Outer Membrane Proteins Molecular Chaperones |
| Zdroj: | 'Nature Communications ', vol: 11, pages: 4948-1-4948-11 (2020) Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-11 (2020) Nature Communications, Nature Publishing Group, 2020, 11 (1), ⟨10.1038/s41467-020-18770-5⟩ Nature Communications, 2020, 11 (1), ⟨10.1038/s41467-020-18770-5⟩ |
| ISSN: | 2041-1723 |
| Popis: | 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. The tripartite multidrug efflux system MexAB-OprM is a major actor in Pseudomonas aeruginosa antibiotic resistance by exporting a large variety of antimicrobial compounds. Here authors present cryo-EM structures of MexB at various stages of the assembly process and provide evidence that MexB activation is mediated by OprM and MexA. |
| Databáze: | OpenAIRE |
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