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Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae

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...

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Detalles Bibliográficos
Autores principales: Nadeem, Aftab, Berg, Alexandra, Pace, Hudson, Alam, Athar, Toh, Eric, Ådén, Jörgen, Zlatkov, Nikola, Myint, Si Lhyam, Persson, Karina, Gröbner, Gerhard, Sjöstedt, Anders, Bally, Marta, Barandun, Jonas, Uhlin, Bernt Eric, Wai, Sun Nyunt
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824476/
https://www.ncbi.nlm.nih.gov/pubmed/35131030
http://dx.doi.org/10.7554/eLife.73439
Descripción
Sumario: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.