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Title | Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from . |
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Journal, issue, pages | Elife, Vol. 11, Year 2022 |
Publish date | Feb 8, 2022 |
Authors | Aftab Nadeem / Alexandra Berg / Hudson Pace / Athar Alam / Eric Toh / Jörgen Ådén / Nikola Zlatkov / Si Lhyam Myint / Karina Persson / Gerhard Gröbner / Anders Sjöstedt / Marta Bally / Jonas Barandun / Bernt Eric Uhlin / Sun Nyunt Wai / |
PubMed 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 . As part ...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 . 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. |
External links | Elife / PubMed:35131030 / PubMed Central |
Methods | EM (helical sym.) |
Resolution | 3.65 Å |
Structure data | EMDB-13185, PDB-7p3r: |
Source |
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Keywords | TOXIN / Pore-forming toxin / Vibrio cholerae |