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PDBsum entry 4pl0
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Transport protein
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PDB id
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4pl0
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References listed in PDB file
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Key reference
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Title
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Structure of an antibacterial peptide ATP-Binding cassette transporter in a novel outward occluded state.
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Authors
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H.G.Choudhury,
Z.Tong,
I.Mathavan,
Y.Li,
S.Iwata,
S.Zirah,
S.Rebuffat,
H.W.Van veen,
K.Beis.
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Ref.
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Proc Natl Acad Sci U S A, 2014,
111,
9145-9150.
[DOI no: ]
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PubMed id
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Abstract
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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.
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