7P3R

Helical structure of the toxin MakA from Vibrio cholera

Summary for 7P3R

• Entry DOI: 10.2210/pdb7p3r/pdb
• EMDB information: 13185
• Descriptor: MakA tetramer (1 entity in total)
• Functional Keywords: pore-forming toxin, vibrio cholerae, toxin
• Biological source: Vibrio cholerae O1 biovar El Tor str. N16961
• Total number of polymer chains: 4
• Total formula weight: 156114.33

Authors

Berg, A.,Nadeem, A.,Uhlin, B.E.,Wai, S.N.,Barandun, J. (deposition date: 2021-07-08, release date: 2022-02-23, Last modification date: 2024-07-17)

Primary citation

Nadeem, A.,Berg, A.,Pace, H.,Alam, A.,Toh, E.,Aden, J.,Zlatkov, N.,Myint, S.L.,Persson, K.,Grobner, G.,Sjostedt, A.,Bally, M.,Barandun, J.,Uhlin, B.E.,Wai, S.N.
Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae .
Elife, 11:-, 2022

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 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.

PubMed: 35131030
DOI: 10.7554/eLife.73439

Experimental method

ELECTRON MICROSCOPY (3.65 Å)