Pore Forming Protein Induced Biomembrane Reorganization and Dynamics: A Focused Review
Pore forming proteins are a broad class of pathogenic proteins secreted by organisms as virulence factors due to their ability to form pores on the target cell membrane. Bacterial pore forming toxins (PFTs) belong to a subclass of pore forming proteins widely implicated in bacterial infections. Alth...
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| Format: | Article |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.737561/full |
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| author | Ilanila Ilangumaran Ponmalar Nirod K. Sarangi Jaydeep K. Basu K. Ganapathy Ayappa K. Ganapathy Ayappa |
| author_facet | Ilanila Ilangumaran Ponmalar Nirod K. Sarangi Jaydeep K. Basu K. Ganapathy Ayappa K. Ganapathy Ayappa |
| author_sort | Ilanila Ilangumaran Ponmalar |
| collection | DOAJ |
| description | Pore forming proteins are a broad class of pathogenic proteins secreted by organisms as virulence factors due to their ability to form pores on the target cell membrane. Bacterial pore forming toxins (PFTs) belong to a subclass of pore forming proteins widely implicated in bacterial infections. Although the action of PFTs on target cells have been widely investigated, the underlying membrane response of lipids during membrane binding and pore formation has received less attention. With the advent of superresolution microscopy as well as the ability to carry out molecular dynamics (MD) simulations of the large protein membrane assemblies, novel microscopic insights on the pore forming mechanism have emerged over the last decade. In this review, we focus primarily on results collated in our laboratory which probe dynamic lipid reorganization induced in the plasma membrane during various stages of pore formation by two archetypal bacterial PFTs, cytolysin A (ClyA), an α-toxin and listeriolysin O (LLO), a β-toxin. The extent of lipid perturbation is dependent on both the secondary structure of the membrane inserted motifs of pore complex as well as the topological variations of the pore complex. Using confocal and superresolution stimulated emission depletion (STED) fluorescence correlation spectroscopy (FCS) and MD simulations, lipid diffusion, cholesterol reorganization and deviations from Brownian diffusion are correlated with the oligomeric state of the membrane bound protein as well as the underlying membrane composition. Deviations from free diffusion are typically observed at length scales below ∼130 nm to reveal the presence of local dynamical heterogeneities that emerge at the nanoscale—driven in part by preferential protein binding to cholesterol and domains present in the lipid membrane. Interrogating the lipid dynamics at the nanoscale allows us further differentiate between binding and pore formation of β- and α-PFTs to specific domains in the membrane. The molecular insights gained from the intricate coupling that occurs between proteins and membrane lipids and receptors during pore formation are expected to improve our understanding of the virulent action of PFTs. |
| first_indexed | 2024-12-23T14:00:19Z |
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| id | doaj.art-de65fb91e4574f64aa5350fb9d0f94bf |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-23T14:00:19Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-de65fb91e4574f64aa5350fb9d0f94bf2022-12-21T17:44:20ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-09-01810.3389/fmolb.2021.737561737561Pore Forming Protein Induced Biomembrane Reorganization and Dynamics: A Focused ReviewIlanila Ilangumaran Ponmalar0Nirod K. Sarangi1Jaydeep K. Basu2K. Ganapathy Ayappa3K. Ganapathy Ayappa4Center for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, IndiaSchool of Chemical Science, Dublin City University, Dublin, IrelandDepartment of Physics, Indian Institute of Science, Bangalore, IndiaCenter for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, IndiaDepartment of Chemical Engineering, Indian Institute of Science, Bengaluru, IndiaPore forming proteins are a broad class of pathogenic proteins secreted by organisms as virulence factors due to their ability to form pores on the target cell membrane. Bacterial pore forming toxins (PFTs) belong to a subclass of pore forming proteins widely implicated in bacterial infections. Although the action of PFTs on target cells have been widely investigated, the underlying membrane response of lipids during membrane binding and pore formation has received less attention. With the advent of superresolution microscopy as well as the ability to carry out molecular dynamics (MD) simulations of the large protein membrane assemblies, novel microscopic insights on the pore forming mechanism have emerged over the last decade. In this review, we focus primarily on results collated in our laboratory which probe dynamic lipid reorganization induced in the plasma membrane during various stages of pore formation by two archetypal bacterial PFTs, cytolysin A (ClyA), an α-toxin and listeriolysin O (LLO), a β-toxin. The extent of lipid perturbation is dependent on both the secondary structure of the membrane inserted motifs of pore complex as well as the topological variations of the pore complex. Using confocal and superresolution stimulated emission depletion (STED) fluorescence correlation spectroscopy (FCS) and MD simulations, lipid diffusion, cholesterol reorganization and deviations from Brownian diffusion are correlated with the oligomeric state of the membrane bound protein as well as the underlying membrane composition. Deviations from free diffusion are typically observed at length scales below ∼130 nm to reveal the presence of local dynamical heterogeneities that emerge at the nanoscale—driven in part by preferential protein binding to cholesterol and domains present in the lipid membrane. Interrogating the lipid dynamics at the nanoscale allows us further differentiate between binding and pore formation of β- and α-PFTs to specific domains in the membrane. The molecular insights gained from the intricate coupling that occurs between proteins and membrane lipids and receptors during pore formation are expected to improve our understanding of the virulent action of PFTs.https://www.frontiersin.org/articles/10.3389/fmolb.2021.737561/fullpore-forming toxinlisteriolysin Ocytolysin Alipid dynamicsfluorescence correlation spectroscopySTED nanoscopy |
| spellingShingle | Ilanila Ilangumaran Ponmalar Nirod K. Sarangi Jaydeep K. Basu K. Ganapathy Ayappa K. Ganapathy Ayappa Pore Forming Protein Induced Biomembrane Reorganization and Dynamics: A Focused Review Frontiers in Molecular Biosciences pore-forming toxin listeriolysin O cytolysin A lipid dynamics fluorescence correlation spectroscopy STED nanoscopy |
| title | Pore Forming Protein Induced Biomembrane Reorganization and Dynamics: A Focused Review |
| title_full | Pore Forming Protein Induced Biomembrane Reorganization and Dynamics: A Focused Review |
| title_fullStr | Pore Forming Protein Induced Biomembrane Reorganization and Dynamics: A Focused Review |
| title_full_unstemmed | Pore Forming Protein Induced Biomembrane Reorganization and Dynamics: A Focused Review |
| title_short | Pore Forming Protein Induced Biomembrane Reorganization and Dynamics: A Focused Review |
| title_sort | pore forming protein induced biomembrane reorganization and dynamics a focused review |
| topic | pore-forming toxin listeriolysin O cytolysin A lipid dynamics fluorescence correlation spectroscopy STED nanoscopy |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.737561/full |
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