Structural Basis for Natural Product Selection and Export by Bacterial ABC Transporters

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Romano, Maria | Fusco, Giuliana | Choudhury, Hassanul, G | Mehmood, Shahid | Robinson, Carol, V | Zirah, Séverine | Hegemann, Julian, D | Lescop, Ewen | Marahiel, Mohamed, A | Rebuffat, Sylvie | de Simone, Alfonso | Beis, Konstantinos

Edité par CCSD ; American Chemical Society -

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.

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