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Structural basis for antibacterial peptide self‐immunity by the bacterial ABC transporter McjD

DOI: 10.15252/embj.201797278 DOI Help

Authors: Kiran Bountra (Imperial College London; Research Complex at Harwell) , Gregor Hagelueken (University of Bonn) , Hassanul Choudhury (Imperial College London; Research Complex at Harwell) , Valentina Corradi (University of Calgary) , Kamel El Omari (University of Oxford) , Armin Wagner (Diamond Light Source) , Indran Mathavan (Imperial College London; Research Complex at Harwell) , Séverine Zirah (Muséum National d'Histoire Naturelle, Sorbonne Universités) , Weixiao Yuan Wahlgren (Imperial College London; Research Complex at Harwell; University of Gothenburg) , D. Peter Tieleman (University of Calgary) , Olav Schiemann (University of Bonn) , Sylvie Rebuffat (Muséum National d'Histoire Naturelle, Sorbonne Universités) , Konstantinos Beis (Imperial College London; Diamond Light Source)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: The Embo Journal

State: Published (Approved)
Published: September 2017
Diamond Proposal Number(s): 8031

Open Access Open Access

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 Escherichia coli. 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 E. coli 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.

Journal Keywords: antibacterial peptide ABC transporter; membrane protein; molecular dynamics; PELDOR; transporter structure

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 04/09/2017 10:58

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embj.201797278.full.pdf

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