5OFR

Structure of the antibacterial peptide ABC transporter McjD in a high energy outward occluded intermediate state

Summary for 5OFR

• Entry DOI: 10.2210/pdb5ofr/pdb
• Descriptor: Microcin-J25 export ATP-binding/permease protein McjD, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: abc transporter, antibacterial peptide, high energy outward occluded intermediate, adp-vo4, membrane protein
• Biological source: Escherichia coli
• Cellular location: Cell inner membrane ; Multi- pass membrane protein : Q9X2W0
• Total number of polymer chains: 2
• Total formula weight: 132097.73

Authors

Beis, K.,Bountra, K. (deposition date: 2017-07-11, release date: 2017-09-06, Last modification date: 2024-01-17)

Primary citation

Bountra, K.,Hagelueken, G.,Choudhury, H.G.,Corradi, V.,El Omari, K.,Wagner, A.,Mathavan, I.,Zirah, S.,Yuan Wahlgren, W.,Tieleman, D.P.,Schiemann, O.,Rebuffat, S.,Beis, K.
Structural basis for antibacterial peptide self-immunity by the bacterial ABC transporter McjD.
EMBO J., 36:3062-3079, 2017

PubMed Abstract: Certain pathogenic bacteria produce and release toxic peptides to ensure either nutrient availability or evasion from the immune system. These peptides are also toxic to the producing bacteria that utilize dedicated ABC transporters to provide self-immunity. The ABC transporter McjD exports the antibacterial peptide MccJ25 in Our previously determined McjD structure provided some mechanistic insights into antibacterial peptide efflux. In this study, we have determined its structure in a novel conformation, apo inward-occluded and a new nucleotide-bound state, high-energy outward-occluded intermediate state, with a defined ligand binding cavity. Predictive cysteine cross-linking in membranes and PELDOR measurements along the transport cycle indicate that McjD does not undergo major conformational changes as previously proposed for multi-drug ABC exporters. Combined with transport assays and molecular dynamics simulations, we propose a novel mechanism for toxic peptide ABC exporters that only requires the transient opening of the cavity for release of the peptide. We propose that shielding of the cavity ensures that the transporter is available to export the newly synthesized peptides, preventing toxic-level build-up.

PubMed: 28864543
DOI: 10.15252/embj.201797278

Experimental method

X-RAY DIFFRACTION (3.4 Å)