Single-particle cryo-EM reveals conformational variability of the oligomeric VCC β-barrel pore in a lipid bilayer

Vibrio cholerae cytolysin (VCC) is a water-soluble, membrane-damaging, pore-forming toxin (PFT) secreted by pathogenic V. cholerae, which causes eukaryotic cell death by altering the plasma membrane permeability. VCC self-assembles on the cell surface and undergoes a dramatic conformational change f...

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Bibliographic Details
Published in:The Journal of cell biology 2021-12, Vol.220 (12), p.1
Main Authors: Sengupta, Nayanika, Mondal, Anish Kumar, Mishra, Suman, Chattopadhyay, Kausik, Dutta, Somnath
Format: Article
Language:English
Subjects:
Amino acids
Atomic structure
Bacterial Proteins - chemistry
Bacterial Proteins - ultrastructure
Cell death
Cell Membrane - metabolism
Cell Membrane - ultrastructure
Cell surface
Cryoelectron Microscopy
High resolution
Lipid bilayers
Lipid Bilayers - chemistry
Lipids
Membrane and lipid biology
Membrane permeability
Membranes
Models, Molecular
Perforin - chemistry
Perforin - metabolism
Perforin - ultrastructure
Pore formation
Protein Multimerization
Protein Structure, Secondary
Structural analysis
Structural Biology
Toxins
Vibrio cholerae - metabolism
Water damage
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Summary:Vibrio cholerae cytolysin (VCC) is a water-soluble, membrane-damaging, pore-forming toxin (PFT) secreted by pathogenic V. cholerae, which causes eukaryotic cell death by altering the plasma membrane permeability. VCC self-assembles on the cell surface and undergoes a dramatic conformational change from prepore to heptameric pore structure. Over the past few years, several high-resolution structures of detergent-solubilized PFTs have been characterized. However, high-resolution structural characterization of small β-PFTs in a lipid environment is still rare. Therefore, we used single-particle cryo-EM to characterize the structure of the VCC oligomer in large unilamellar vesicles, which is the first atomic-resolution cryo-EM structure of VCC. From our study, we were able to provide the first documented visualization of the rim domain amino acid residues of VCC interacting with lipid membrane. Furthermore, cryo-EM characterization of lipid bilayer-embedded VCC suggests interesting conformational variabilities, especially in the transmembrane channel, which could have a potential impact on the pore architecture and assist us in understanding the pore formation mechanism.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.202102035