Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae
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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/73439 |
| _version_ | 1811252858789560320 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Aftab Nadeem |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T16:41:01Z |
| format | Article |
| id | doaj.art-0a8dd6b4c732412e88ada5ed73ee8d45 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:41:01Z |
| publishDate | 2022-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0a8dd6b4c732412e88ada5ed73ee8d452022-12-22T03:24:46ZengeLife Sciences Publications LtdeLife2050-084X2022-02-011110.7554/eLife.73439Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio choleraeAftab Nadeem0https://orcid.org/0000-0002-1439-6216Alexandra Berg1https://orcid.org/0000-0003-3609-2878Hudson Pace2https://orcid.org/0000-0001-5116-2577Athar Alam3https://orcid.org/0000-0001-8773-7598Eric Toh4https://orcid.org/0000-0002-0103-0696Jörgen Ådén5https://orcid.org/0000-0002-4480-1219Nikola Zlatkov6https://orcid.org/0000-0003-3318-9084Si Lhyam Myint7https://orcid.org/0000-0001-5384-3691Karina Persson8https://orcid.org/0000-0003-0807-0348Gerhard Gröbner9https://orcid.org/0000-0001-7380-8797Anders Sjöstedt10https://orcid.org/0000-0002-0768-8405Marta Bally11https://orcid.org/0000-0002-5865-8302Jonas Barandun12https://orcid.org/0000-0003-2971-8190Bernt Eric Uhlin13https://orcid.org/0000-0002-2991-8072Sun Nyunt Wai14https://orcid.org/0000-0003-4793-4671Department of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, SwedenDepartment of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden; Science for Life Laboratory (SciLifeLab), Department of Molecular Biology, Umeå University, Umeå, SwedenUmeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; Department of Clinical Microbiology, Umeå University, Umeå, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, SwedenUmeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden; Department of Clinical Microbiology, Umeå University, Umeå, SwedenDepartment of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, SwedenUmeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; Department of Chemistry, Umeå University, Umeå, SwedenDepartment of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, SwedenDepartment of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, SwedenUmeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; Department of Chemistry, Umeå University, Umeå, SwedenUmeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; Department of Chemistry, Umeå University, Umeå, SwedenUmeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden; Department of Clinical Microbiology, Umeå University, Umeå, SwedenUmeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; Department of Clinical Microbiology, Umeå University, Umeå, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, SwedenDepartment of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, SwedenDepartment of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, SwedenDepartment of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, SwedenThe 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.https://elifesciences.org/articles/73439Vibrio choleraeMakAlipid |
| spellingShingle | 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 Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae eLife Vibrio cholerae MakA lipid |
| title | Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae |
| title_full | Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae |
| title_fullStr | Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae |
| title_full_unstemmed | Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae |
| title_short | Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae |
| title_sort | protein lipid interaction at low ph induces oligomerization of the maka cytotoxin from vibrio cholerae |
| topic | Vibrio cholerae MakA lipid |
| url | https://elifesciences.org/articles/73439 |
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