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.
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6 December 2021
Article|
October 07 2021
Single-particle cryo-EM reveals conformational variability of the oligomeric VCC β-barrel pore in a lipid bilayer
Nayanika Sengupta
,
Nayanika Sengupta
1
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India
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Anish Kumar Mondal
,
Anish Kumar Mondal
2
Centre for Protein Science, Design and Engineering, Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Punjab, India
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Suman Mishra
,
Suman Mishra
1
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India
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Kausik Chattopadhyay
,
Kausik Chattopadhyay
2
Centre for Protein Science, Design and Engineering, Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Punjab, India
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Somnath Dutta
1
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India
Correspondence to Somnath Dutta: somnath@iisc.ac.in
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Nayanika Sengupta
1
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India
Anish Kumar Mondal
2
Centre for Protein Science, Design and Engineering, Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Punjab, India
Suman Mishra
1
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India
Kausik Chattopadhyay
2
Centre for Protein Science, Design and Engineering, Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Punjab, India
Correspondence to Somnath Dutta: somnath@iisc.ac.in
Received:
February 15 2021
Revision Received:
August 25 2021
Accepted:
September 19 2021
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding
Funder(s):
Department of Biotechnology, Ministry of Science and Technology, India
Funder(s):
Department of Science and Technology, Ministry of Science and Technology, India
Funder(s):
Ministry of Human Resource Development
Funder(s):
Indian Institute of Science Education and Research Mohali
Funder(s):
DBT-BUILDER
- Award Id(s): BT/INF/22/SP22844/2017
Funder(s):
DST-FIST
- Award Id(s): SR/FST/LSII-039/2015
Funder(s):
Ministry of Human Resource Development
- Award Id(s): STARS-1/171
Funder(s):
Science and Engineering Research Board
- Award Id(s): SB/S2/RJN-145/2015,SERB-EMR/2016/000608
Funder(s):
DBT
- Award Id(s): BT/PR25580/BRB/10/1619/2017
© 2021 Sengupta et al.
2021
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2021) 220 (12): e202102035.
Article history
Received:
February 15 2021
Revision Received:
August 25 2021
Accepted:
September 19 2021
Citation
Nayanika Sengupta, Anish Kumar Mondal, Suman Mishra, Kausik Chattopadhyay, Somnath Dutta; Single-particle cryo-EM reveals conformational variability of the oligomeric VCC β-barrel pore in a lipid bilayer. J Cell Biol 6 December 2021; 220 (12): e202102035. doi: https://doi.org/10.1083/jcb.202102035
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