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

Autor: Bountra, K, Hagelueken, G, Choudhury, H, Corradi, V, El Omari, K, Wagner, A, Mathavan, I, Zirah, S, Yuan Wahlgren, W, Tieleman, D, Schiemann, O, Rebuffat, S, Beis, K
Přispěvatelé: Medical Research Council (MRC)
Rok vydání: 2017
Předmět:
Models
Molecular
Biochemistry & Molecular Biology
MOLECULAR-DYNAMICS SIMULATIONS
Protein Conformation
SOFTWARE
Molecular Dynamics Simulation
Crystallography
X-Ray
Article
Bacteriocins
PELDOR
Structural Biology
BINDING CASSETTE TRANSPORTER
Escherichia coli
CRYSTAL-STRUCTURE
membrane protein
Membrane & Intracellular Transport
ATP-BINDING
MAXIMUM-LIKELIHOOD
LIPID-BILAYERS
11 Medical and Health Sciences
Science & Technology
transporter structure
Escherichia coli Proteins
MACROMOLECULAR CRYSTALLOGRAPHY
Cell Biology
Articles
06 Biological Sciences
antibacterial peptide ABC transporter
molecular dynamics
Microbiology
Virology & Host Pathogen Interaction
Protein Transport
FORCE-FIELD
ATP-Binding Cassette Transporters
08 Information and Computing Sciences
Life Sciences & Biomedicine
MICROCIN J25
Developmental Biology
Zdroj: The EMBO Journal
ISSN: 1460-2075
Popis: 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.
Databáze: OpenAIRE
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