1. Membrane insertion of α-xenorhabdolysin in near-atomic detail
- Author
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Ingrid R. Vetter, Evelyn Schubert, Daniel Prumbaum, Pawel A. Penczek, and Stefan Raunser
- Subjects
0301 basic medicine ,Pore complex ,Protein Conformation ,Cryo-electron microscopy ,Structural Biology and Molecular Biophysics ,xenorhabdus ,bi-component toxin ,Crystal structure ,Crystallography, X-Ray ,Cell membrane ,chemistry.chemical_compound ,0302 clinical medicine ,Protein structure ,Biology (General) ,pore-forming toxin ,Host cell membrane ,Microbiology and Infectious Disease ,0303 health sciences ,Pore-forming toxin ,Membrane insertion ,Chemistry ,General Neuroscience ,General Medicine ,Transmembrane protein ,3. Good health ,Monomer ,medicine.anatomical_structure ,Medicine ,medicine.symptom ,Research Article ,Pore Forming Cytotoxic Proteins ,xenorhabdolysin ,QH301-705.5 ,Science ,Bacterial Toxins ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Bacterial Proteins ,None ,medicine ,structure ,030304 developmental biology ,General Immunology and Microbiology ,Activator (genetics) ,Cell Membrane ,Cryoelectron Microscopy ,030104 developmental biology ,Mechanism of action ,Structural biology ,Biophysics ,cryo-EM ,Protein Multimerization ,ddc:600 ,030217 neurology & neurosurgery - Abstract
eLife 7, e38017 (2018). doi:10.7554/eLife.38017, α-Xenorhabdolysins (Xax) are α-pore-forming toxins (α-PFT) that form 1–1.3 MDa large pore complexes to perforate the host cell membrane. PFTs are used by a variety of bacterial pathogens to attack host cells. Due to the lack of structural information, the molecular mechanism of action of Xax toxins is poorly understood. Here, we report the cryo-EM structure of the XaxAB pore complex from Xenorhabdus nematophila and the crystal structures of the soluble monomers of XaxA and XaxB. The structures reveal that XaxA and XaxB are built similarly and appear as heterodimers in the 12–15 subunits containing pore, classifying XaxAB as bi-component α-PFT. Major conformational changes in XaxB, including the swinging out of an amphipathic helix are responsible for membrane insertion. XaxA acts as an activator and stabilizer for XaxB that forms the actual transmembrane pore. Based on our results, we propose a novel structural model for the mechanism of Xax intoxication., Published by eLife Sciences Publications, Cambridge
- Published
- 2018
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