Structural highlights
Publication Abstract from PubMedThe alpha-pore-forming toxins (alpha-PFTs) from pathogenic bacteria damage host cell membranes by pore formation. We demonstrate a remarkable, hitherto unknown mechanism by an alpha-PFT protein from Vibrio cholerae. As part of the MakA/B/E tripartite toxin, MakA is involved in membrane pore formation similar to other alpha-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 A 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 alpha-PFT conformation. Our study provides insights into a novel tubulation mechanism of an alpha-PFT protein and a new mode of action by a secreted bacterial toxin. Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae.,Nadeem A, Berg A, Pace H, Alam A, Toh E, Aden J, Zlatkov N, Myint SL, Persson K, Grobner G, Sjostedt A, Bally M, Barandun J, Uhlin BE, Wai SN Elife. 2022 Feb 8;11. pii: 73439. doi: 10.7554/eLife.73439. PMID:35131030[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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