1. Structural Basis for Natural Product Selection and Export by Bacterial ABC Transporters
- Author
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Giuliana Fusco, Ewen Lescop, Sylvie Rebuffat, Julian D. Hegemann, Shahid Mehmood, Carol V. Robinson, Maria Romano, Konstantinos Beis, Séverine Zirah, Hassanul G. Choudhury, Alfonso De Simone, Mohamed A. Marahiel, Dipartimento di Biologia (Universita degli Studi di Milano), Università degli studi di Milano [Milano], Department of Mechanical Engineering, University of Engineering & Technology, Taxila, Loughborough University, Mathematics Education Centre, Loughborough, United Kingdom, Molécules de Communication et Adaptation des Micro-Organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS), Department of Life Sciences, Imperial College London, Respiratory Epidemiology and Public Health, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], Medical Research Council (MRC), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Life Sciences, Imperial College London, London, United Kingdom, Department of Chemistry, University of Oxford, Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), LOEWE Center for Synthetic Microbiology, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), LOEWE Center for Synthetic Microbiology, Philipps-Universität Marburg, Rutherford Appleton Laboratory, Research Complex at Harwell, Romano, M., Fusco, G., Choudhury, H. G., Mehmood, S., Robinson, C. V., Zirah, S., Hegemann, J. D., Lescop, E., Marahiel, M. A., Rebuffat, S., De Simone, A., and Beis, K.
- Subjects
0301 basic medicine ,ALPHA-SYNUCLEIN ,Protein Conformation ,[SDV]Life Sciences [q-bio] ,PROTEIN ,Peptide ,ATP-binding cassette transporter ,Plasma protein binding ,medicine.disease_cause ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Protein structure ,FUNCTIONAL-CHARACTERIZATION ,Bacteriocins ,BINDING CASSETTE TRANSPORTER ,ComputingMilieux_MISCELLANEOUS ,chemistry.chemical_classification ,biology ,Chemistry ,Escherichia coli Proteins ,General Medicine ,Anti-Bacterial Agents ,Protein Transport ,I-III ,Molecular Medicine ,03 Chemical Sciences ,Life Sciences & Biomedicine ,MICROCIN J25 ,Protein Binding ,Biochemistry & Molecular Biology ,LASSO PEPTIDES ,Computational biology ,010402 general chemistry ,03 medical and health sciences ,Bacteriocin ,[CHIM.ANAL]Chemical Sciences/Analytical chemistry ,medicine ,Escherichia coli ,[CHIM]Chemical Sciences ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,SATURATION-TRANSFER DIFFERENCE ,Nuclear Magnetic Resonance, Biomolecular ,Science & Technology ,Natural product ,Organic Chemistry ,MASS-SPECTROMETRY ,06 Biological Sciences ,biology.organism_classification ,MOLECULAR-MECHANISM ,0104 chemical sciences ,030104 developmental biology ,ATP-Binding Cassette Transporters ,Bacteria - Abstract
International audience; Bacteria under stress produce ribosomally synthesized and post-translationally modified peptides(RiPPs) to target closely related species, such as the lasso peptide microcin J25 (MccJ25). These peptides are also toxicto the producing organisms that utilize dedicated ABC transporters to achieve self-immunity. MccJ25 is exported bythe Escherichia coli ABC transporter McjD through a complex mechanism of recognition that has remained elusive. Here, we used biomolecular NMR to study this interaction and identified a region of the toxic peptide that is crucial to itsrecognition by the ABC transporter. Our study provides evidence that McjD is highly specific to MccJ25 and not toother RiPPs or antibiotics, unlike multidrug ABC transporters. Additionally, we show that MccJ25 is not exported by anothernatural product ABC transporter. Therefore, we propose that specific interactions between natural product ABC transporters and their substrate provides them with their high degree of specificity. Taken together, these findings suggest that ABC transporters might have acquired structural elements in their binding cavity to recognize and allow promiscuous export of a larger variety of compounds.
- Published
- 2018
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