Sequence Diversity in the Pore-Forming Motifs of the Membrane-Damaging Protein Toxins

Mondal, Anish Kumar; Verma, Pratima; Lata, Kusum; Singh, Mahendra; Chatterjee, Shamaita; Chattopadhyay, Kausik

doi:10.1007/s00232-020-00141-2

Cited by 10 publications

(6 citation statements)

References 62 publications

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“…PFTs exhibit diverse structures and are typically classified according to the secondary structure of the transmembrane region (Table 1). Produced as soluble monomers, PFTs oligomerize upon interaction with the target membrane and undergo structural rearrangements that allow them to form mature transmembrane pores ( Figure 3; [29][30][31]63]). The purpose of PFT secretion depends on the organism: bacteria may use them as virulence factors, while eukaryotes usually employ PFT as part of a defense mechanism [64].…”

Section: Most Frequently Employed Pores: Pore-forming Toxinsmentioning

confidence: 99%

Biological Nanopores: Engineering on Demand

Crnković

Srnko

Anderluh

2021

Life

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Nanopore-based sensing is a powerful technique for the detection of diverse organic and inorganic molecules, long-read sequencing of nucleic acids, and single-molecule analyses of enzymatic reactions. Selected from natural sources, protein-based nanopores enable rapid, label-free detection of analytes. Furthermore, these proteins are easy to produce, form pores with defined sizes, and can be easily manipulated with standard molecular biology techniques. The range of possible analytes can be extended by using externally added adapter molecules. Here, we provide an overview of current nanopore applications with a focus on engineering strategies and solutions.

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Section: Most Frequently Employed Pores: Pore-forming Toxinsmentioning

confidence: 99%

Biological Nanopores: Engineering on Demand

Crnković

Srnko

Anderluh

2021

Life

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“…Gasdermin D is another distinct PFP that plays crucial roles in the inflammatory cell death or pyroptosis in the mammalian system ( Lieberman et al, 2019 ). PFTs and PFPs from the diverse kingdoms of life share very little or no similarity in their amino acid sequences, and they highlight enormous variations in their structures and mechanisms of actions ( Mondal et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Curcumin Inhibits Membrane-Damaging Pore-Forming Function of the β-Barrel Pore-Forming Toxin Vibrio cholerae Cytolysin

et al. 2022

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Vibrio cholerae cytolysin (VCC) is a β-barrel pore-forming toxin (β-PFT). Upon encountering the target cells, VCC forms heptameric β-barrel pores and permeabilizes the cell membranes. Structure-function mechanisms of VCC have been extensively studied in the past. However, the existence of any natural inhibitor for VCC has not been reported yet. In the present study, we show that curcumin can compromise the membrane-damaging activity of VCC. Curcumin is known to modulate a wide variety of biological processes and functions. However, the application of curcumin in the physiological scenario often gets limited due to its extremely poor solubility in the aqueous environment. Interestingly, we find that VCC can associate with the insoluble fraction of curcumin in the aqueous medium and thus gets separated from the solution phase. This, in turn, reduces the availability of VCC to attack the target membranes and thus blocks the membrane-damaging action of the toxin. We also observe that the soluble aqueous extract of curcumin, generated by the heat treatment, compromises the pore-forming activity of VCC. Interestingly, in the presence of such soluble extract of curcumin, VCC binds to the target membranes and forms the oligomeric assembly. However, such oligomers appear to be non-functional, devoid of the pore-forming activity. The ability of curcumin to bind to VCC and neutralize its membrane-damaging activity suggests that curcumin has the potential to act as an inhibitor of this potent bacterial β-PFT.

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“…Pore-forming proteins form conduits in cell plasma membranes, allowing intracellular and extracellular solutes to leak across cell boundaries. Although the amino acid sequences and three-dimensional structures of pore-forming proteins are extremely diverse, they share a common mode of action in which water-soluble monomers come together to form oligomeric pre-pore structures that insert into membranes to form pores 1 . Many pore formers originating from pathogenic bacteria are well documented to be toxic against agricultural pests 2 , 3 .…”

Section: Introductionmentioning

confidence: 99%

A deep learning model to detect novel pore-forming proteins

Jacob

Kahn

2022

Sci Rep

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Many pore-forming proteins originating from pathogenic bacteria are toxic against agricultural pests. They are the key ingredients in several pesticidal products for agricultural use, including transgenic crops. There is an urgent need to identify novel pore-forming proteins to combat development of resistance in pests to existing products, and to develop products that are effective against a broader range of pests. Existing computational methodologies to search for these proteins rely on sequence homology-based approaches. These approaches are based on similarities between protein sequences, and thus are limited in their usefulness for discovering novel proteins. In this paper, we outline a novel deep learning model trained on pore-forming proteins from the public domain. We compare different ways of encoding protein information during training, and contrast it with traditional approaches. We show that our model is capable of identifying known pore formers with no sequence similarity to the proteins used to train the model, and therefore holds promise for identifying novel pore formers.

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Sequence Diversity in the Pore-Forming Motifs of the Membrane-Damaging Protein Toxins

Cited by 10 publications

References 62 publications

Biological Nanopores: Engineering on Demand

Biological Nanopores: Engineering on Demand

Curcumin Inhibits Membrane-Damaging Pore-Forming Function of the β-Barrel Pore-Forming Toxin Vibrio cholerae Cytolysin

A deep learning model to detect novel pore-forming proteins

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