title: Membrane insertion of a Tc toxin in near-atomic detail.
abstract: Tc toxins from pathogenic bacteria use a special syringe-like mechanism to perforate the host cell membrane and inject a deadly enzyme into the host cytosol. The molecular mechanism of this unusual injection system is poorly understood. Using electron cryomicroscopy, we determined the structure of TcdA1 from Photorhabdus luminescens embedded in lipid nanodiscs. In our structure, compared with the previous structure of TcdA1 in the prepore state, the transmembrane helices rearrange in the membrane and open the initially closed pore. However, the helices do not span the complete membrane; instead, the loops connecting the helices form the rim of the funnel. Lipid head groups reach into the space between the loops and consequently stabilize the pore conformation. The linker domain is folded and packed into a pocket formed by the other domains of the toxin, thereby considerably contributing to stabilization of the pore state.
authors: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors: Christos
authors: C
authors: Gatsogiannis
authors: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors: Felipe
authors: F
authors: Merino
authors: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors: Daniel
authors: D
authors: Prumbaum
authors: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors: Daniel
authors: D
authors: Roderer
authors: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors: Franziska
authors: F
authors: Leidreiter
authors: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors: Dominic
authors: D
authors: Meusch
authors: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors: Stefan
authors: S
authors: Raunser
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D001427:Bacterial Toxins / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry*; D008958:Models, Molecular; D020637:Photorhabdus / Q000737:chemistry*; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D008563:Membrane Lipids; D052899:Pore Forming Cytotoxic Proteins