Imperial College London

ProfessorAlfonsoDe Simone

Faculty of Natural SciencesDepartment of Life Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3052a.de-simon Website

 
 
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Location

 

603Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Romano:2018:10.1021/acschembio.8b00226,
author = {Romano, M and Fusco, G and Choudhury, H and Mehmood, S and Robinson, C and Zirah, S and Hegemann, J and Lescop, E and Marahiel, M and Rebuffat, S and De, Simone A and Beis, K},
doi = {10.1021/acschembio.8b00226},
journal = {ACS Chemical Biology},
pages = {1598--1609},
title = {Structural basis for natural product selection and export by bacterial ABC transporters},
url = {http://dx.doi.org/10.1021/acschembio.8b00226},
volume = {13},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - 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 toxic to the producing organisms that utilize dedicated ABC transporters to achieve self-immunity. MccJ25 is exported by the 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 its recognition by the ABC transporter. Our study provides evidence that McjD is highly specific to MccJ25 and not to other RiPPs or antibiotics, unlike multidrug ABC transporters. Additionally, we show that MccJ25 is not exported by another natural 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.
AU - Romano,M
AU - Fusco,G
AU - Choudhury,H
AU - Mehmood,S
AU - Robinson,C
AU - Zirah,S
AU - Hegemann,J
AU - Lescop,E
AU - Marahiel,M
AU - Rebuffat,S
AU - De,Simone A
AU - Beis,K
DO - 10.1021/acschembio.8b00226
EP - 1609
PY - 2018///
SN - 1554-8929
SP - 1598
TI - Structural basis for natural product selection and export by bacterial ABC transporters
T2 - ACS Chemical Biology
UR - http://dx.doi.org/10.1021/acschembio.8b00226
UR - http://hdl.handle.net/10044/1/60065
VL - 13
ER -