Structural highlights
Function
[MCJD_ECOLX] Is able to protect a cell, which harbors the plasmid pTUC100 encoding microcin J25, against microcin J25. Is required for microcin J25 export out of the producing cells.[1] [2]
Publication Abstract from PubMed
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-A 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.
Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state.,Choudhury HG, Tong Z, Mathavan I, Li Y, Iwata S, Zirah S, Rebuffat S, van Veen HW, Beis K Proc Natl Acad Sci U S A. 2014 Jun 11. pii: 201320506. PMID:24920594[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Solbiati JO, Ciaccio M, Farias RN, Gonzalez-Pastor JE, Moreno F, Salomon RA. Sequence analysis of the four plasmid genes required to produce the circular peptide antibiotic microcin J25. J Bacteriol. 1999 Apr;181(8):2659-62. PMID:10198038
- ↑ Solbiati JO, Ciaccio M, Farias RN, Salomon RA. Genetic analysis of plasmid determinants for microcin J25 production and immunity. J Bacteriol. 1996 Jun;178(12):3661-3. PMID:8655570
- ↑ Choudhury HG, Tong Z, Mathavan I, Li Y, Iwata S, Zirah S, Rebuffat S, van Veen HW, Beis K. Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state. Proc Natl Acad Sci U S A. 2014 Jun 11. pii: 201320506. PMID:24920594 doi:http://dx.doi.org/10.1073/pnas.1320506111
