Department of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden
Department of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden; Science for Life Laboratory (SciLifeLab), Department of Molecular Biology, Umeå University, Umeå, Sweden
Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; Department of Clinical Microbiology, Umeå University, Umeå, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden; Department of Clinical Microbiology, Umeå University, Umeå, Sweden
Department of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden
Department of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden
Department of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden
Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden; Department of Clinical Microbiology, Umeå University, Umeå, Sweden
Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; Department of Clinical Microbiology, Umeå University, Umeå, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
Department of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden
Department of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden
Department of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden
The α-pore-forming toxins (α-PFTs) from pathogenic bacteria damage host cell membranes by pore formation. We demonstrate a remarkable, hitherto unknown mechanism by an α-PFT protein from Vibrio cholerae. As part of the MakA/B/E tripartite toxin, MakA is involved in membrane pore formation similar to other α-PFTs. In contrast, MakA in isolation induces tube-like structures in acidic endosomal compartments of epithelial cells in vitro. The present study unravels the dynamics of tubular growth, which occurs in a pH-, lipid-, and concentration-dependent manner. Within acidified organelle lumens or when incubated with cells in acidic media, MakA forms oligomers and remodels membranes into high-curvature tubes leading to loss of membrane integrity. A 3.7 Å cryo-electron microscopy structure of MakA filaments reveals a unique protein-lipid superstructure. MakA forms a pinecone-like spiral with a central cavity and a thin annular lipid bilayer embedded between the MakA transmembrane helices in its active α-PFT conformation. Our study provides insights into a novel tubulation mechanism of an α-PFT protein and a new mode of action by a secreted bacterial toxin.
