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@article{Choudhury:2014:10.1073/pnas.1320506111,
author = {Choudhury, HG and Tong, Z and Mathavan, I and Li, Y and Iwata, S and Zirah, S and Rebuffat, S and van, Veen HW and Beis, K},
doi = {10.1073/pnas.1320506111},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
pages = {9145--9150},
title = {Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state},
url = {http://dx.doi.org/10.1073/pnas.1320506111},
volume = {111},
year = {2014}
}

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TY - JOUR
AB - Enterobacteriaceae produce antimicrobial peptides for survival under nutrient starvation. Microcin J25 (MccJ25) is an antimicrobial peptide with a unique lasso topology. It is secreted by the ATP-binding cassette (ABC) exporter McjD, which ensures self-immunity of the producing strain through efficient export of the toxic mature peptide from the cell. Here we have determined the crystal structure of McjD from Escherichia coli at 2.7-Å resolution, which is to the authors’ knowledge the first structure of an antibacterial peptide ABC transporter. Our functional and biochemical analyses demonstrate McjD-dependent immunity to MccJ25 through efflux of the peptide. McjD can directly bind MccJ25 and displays a basal ATPase activity that is stimulated by MccJ25 in both detergent solution and proteoliposomes. McjD adopts a new conformation, termed nucleotide-bound outward occluded. The new conformation defines a clear cavity; mutagenesis and ligand binding studies of the cavity have identified Phe86, Asn134, and Asn302 as important for recognition of MccJ25. Comparisons with the inward-open MsbA and outward-open Sav1866 structures show that McjD has structural similarities with both states without the intertwining of transmembrane (TM) helices. The occluded state is formed by rotation of TMs 1 and 2 toward the equivalent TMs of the opposite monomer, unlike Sav1866 where they intertwine with TMs 3–6 of the opposite monomer. Cysteine cross-linking studies on the McjD dimer in inside-out membrane vesicles of E. coli confirmed the presence of the occluded state. We therefore propose that the outward-occluded state represents a transition intermediate between the outward-open and inward-open conformation of ABC exporters.
AU - Choudhury,HG
AU - Tong,Z
AU - Mathavan,I
AU - Li,Y
AU - Iwata,S
AU - Zirah,S
AU - Rebuffat,S
AU - van,Veen HW
AU - Beis,K
DO - 10.1073/pnas.1320506111
EP - 9150
PY - 2014///
SN - 0027-8424
SP - 9145
TI - Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state
T2 - Proceedings of the National Academy of Sciences of the United States of America
UR - http://dx.doi.org/10.1073/pnas.1320506111
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000337760600042&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - https://www.pnas.org/content/111/25/9145
VL - 111
ER -

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