Conformational snapshots of the bacitracin sensing and resistance transporter BceAB

Antimicrobial peptides are diverse molecules that include powerful medications such as bacitracin and vancomycin, as well as potent bacterial signaling molecules. Several antimicrobial peptides elicit cell death in gram-positive species by binding to lipid II cycle intermediates and inhibiting the synthesis of peptidoglycan. Many gram-positive organisms have evolved an elegant mechanism to sense and resist such antimicrobial peptides. In these organisms, a “Bce-type” adenosine triphosphate–binding cassette (ABC) transporter forms a protein complex with a two-component system, and together these components sense and provide resistance to antimicrobial peptides present at the cell surface. Conformational switching of Bce-type transporters is proposed to be the stimulus that activates the associated two-component system through a novel flux-sensing mechanism. In this work, we determined the detergent-solubilized structure of the Bce-type ABC transporter BceAB from Bacillus subtilis in two distinct conformational states using cryo–electron microscopy. Together with mass spectrometry and enzymatic data, our structures reveal the overall architecture of the Bce-type transporter family, uncover a specialized lipid-binding pocket for lipid II cycle intermediates, and reveal the conformational changes that are proposed to initiate signaling through the associated two-component system.