We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae.
- Authors
Nadeem, Aftab; Berg, Alexandra; Pace, Hudson; Alam, Athar; Toh, Eric; Ådén, Jörgen; Zlatkov, Nikola; Si Lhyam Myint; Persson, Karina; Gröbner, Gerhard; Sjöstedt, Anders; Bally, Marta; Barandun, Jonas; Uhlin, Bernt Eric; Sun Nyunt Wai
- Abstract
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.
- Subjects
VIBRIO cholerae; PROTEIN-lipid interactions; CELL membrane formation; BACTERIAL toxins; OLIGOMERIZATION; PATHOGENIC bacteria; TOXINS
- Publication
eLife, 2022, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.73439