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

eLife, ISSN: 2050-084X, Vol: 11
2022
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Structural mechanism of membrane remodeling caused by the protein MakA from Vibrio cholerae

Research performed at Umeå University has led to the discovery of a pH-induced structural mechanism of membrane remodeling caused by the protein MakA, a subunit of the recently described α-pore-forming toxin from the pathogenic bacterium Vibrio cholerae. Collaborating scientists affiliated with MIMS and UCMR publish their new findings in the journal eLife.

Article Description

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.

Bibliographic Details

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

eLife Sciences Publications, Ltd

Neuroscience; Biochemistry, Genetics and Molecular Biology; Immunology and Microbiology

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