Structures and functions of the membrane-damaging pore-forming proteins

Mondal, Anish Kumar; Chattopadhyay, Kausik

doi:10.1016/bs.apcsb.2021.07.001

Cited by 7 publications

(4 citation statements)

References 197 publications

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“…PFTs are usually synthesized as water-soluble molecules that penetrate the membrane in monomeric form [4] and are formed into oligomeric pores within the membranes at the interaction with target cells' membranes. Despite the slight similarity of the PFTs' primary sequences, one of the families of these proteins, namely the β-barrel PFTs, demonstrate not only a conformational similarity but also the universality of the functional mechanisms of action of these toxins [5]. Comparison of the amino acid sequences of β-PFTs with the Bacillus cereus Lys171-Gly250 hemolysin II (HlyII) sequence [6] revealed in their primary structures a peptide region with a high degree of homology to this peptide that we called "homologous peptide", which contains an identical sequence YGNQLFM.…”

Section: Introductionmentioning

confidence: 99%

A High-Homology Region in Bacterial β-Barrel Pore-Forming Toxins

Nagel,

Vetrova,

Rudenko

et al. 2024

Preprint

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Pathogenicity of many bacteria including Bacillus cereus and Staphylococcus aureus depends on pore-forming toxins (PFTs), which cause lysis of host cells by forming pores in membranes of eukaryotic cells. Bioinformatic analysis revealed in over 600 PFTs a region homologous to the Lys171-Gly250 sequence in hemolysin II (HlyII) from B. cereus, which we designated as “homologous peptide”. Three β-barrel PFTs were used for a detailed comparative analysis. Two of them –HlyII and cytotoxin K2 (CytK2), – are synthesized in Bacillus cereus sensu lato; the third – S. aureus α-toxin (Hla) – is the most investigated representative of the family. Protein modeling showed certain amino acids of homologous peptide to be located on the surface of the monomeric forms of these β-barrel PFTs. We obtained monoclonal antibodies against both a cloned homologous peptide and a 14-membered synthetic peptide DSFNTFYGNQLFMK as part of homologous peptide. The HlyII, CytK2 and Hla regions recognized by the obtained antibodies, as well as an antibody capable of suppressing the hemolytic activity of CytK2, were identified in the course of the work. Antibodies capable of recognizing PFTs of various origins can be useful tools for both identification and suppression of the cytolytic activity of PFTs.

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Section: Introductionmentioning

confidence: 99%

A High-Homology Region in Bacterial β-Barrel Pore-Forming Toxins

Nagel,

Vetrova,

Rudenko

et al. 2024

Preprint

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“…Cholesterol-dependent cytolysins (CDCs) are a large family of bacterial poreforming proteins (PFPs) that play significant roles in virulence [1][2][3][4][5][6][7] . These PFPs bind to the bilayer as monomers, self-assemble into prepore intermediates on the bilayer surface, and then cooperatively insert into the bilayer to form membrane-spanning pores complexes 8,9 .…”

Section: Introductionmentioning

confidence: 99%

Perfringolysin O pore-forming complexes are predominantly integral multiples of six subunits

Liu,

Qin,

Luo

et al. 2024

Preprint

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Perfringolysin O is a well-studied bacterial cytolysin that forms large oligomeric pores with a wide range of sizes on membranes via a prepore intermediate. Here we examined the sizes of both PFO prepore and pore complexes electrophoretically using a multi-stack-gradient gel and found that, unexpectedly, there are only at most seven predominant sizes of either pores or prepores. Complexes extracted from each band exhibit contour lengths that are integral multiples of six subunits. High-resolution atomic force microscopy images of PFO pore complexes in supported bilayers also reveal a predominant hexameric-based stoichiometry. Thus, these results reveal a previously unknown structural hierarchy in PFO complexes, with larger complexes apparently built up from hexameric sub-complexes. We suggest that different inter-subunit interactions within and between the hexamers result in a likewise difference in the coordination of the prepore-to-pore transition within and between the hexamers, and is thus a critical feature of the allostery of this large multi-subunit complex.

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“…PFTs are usually synthesized as water-soluble molecules that penetrate the membrane in monomeric form and are formed into oligomeric pores within the membrane upon interaction with the membranes of target cells [4,5]. Despite the slight similarity of PFTs' primary sequences, one of the families of these proteins, namely, β-barrel PFTs, demonstrates not only the conformational similarity, but also the universality of the functional mechanisms of action of these toxins [6]. Comparison of the amino acid sequences of β-PFTs with the Bacillus cereus Lys171-Gly250 hemolysin II (HlyII) sequence revealed, in their primary structures, a peptide region with a high degree of homology to this peptide that we called a "homologous peptide" (HP), which contains the identical sequence 219YGNQLFM225 (according to the HlyII sequence) [7].…”

Section: Introductionmentioning

confidence: 99%

A High-Homology Region Provides the Possibility of Detecting β-Barrel Pore-Forming Toxins from Various Bacterial Species

Nagel,

Vetrova,

Rudenko

et al. 2024

IJMS

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The pathogenicity of many bacteria, including Bacillus cereus and Staphylococcus aureus, depends on pore-forming toxins (PFTs), which cause the lysis of host cells by forming pores in the membranes of eukaryotic cells. Bioinformatic analysis revealed a region homologous to the Lys171-Gly250 sequence in hemolysin II (HlyII) from B. cereus in over 600 PFTs, which we designated as a “homologous peptide”. Three β-barrel PFTs were used for a detailed comparative analysis. Two of them—HlyII and cytotoxin K2 (CytK2)—are synthesized in Bacillus cereus sensu lato; the third, S. aureus α-toxin (Hla), is the most investigated representative of the family. Protein modeling showed certain amino acids of the homologous peptide to be located on the surface of the monomeric forms of these β-barrel PFTs. We obtained monoclonal antibodies against both a cloned homologous peptide and a 14-membered synthetic peptide, DSFNTFYGNQLFMK, as part of the homologous peptide. The HlyII, CytK2, and Hla regions recognized by the obtained antibodies, as well as an antibody capable of suppressing the hemolytic activity of CytK2, were identified in the course of this work. Antibodies capable of recognizing PFTs of various origins can be useful tools for both identification and suppression of the cytolytic activity of PFTs.

show abstract

Structures and functions of the membrane-damaging pore-forming proteins

Cited by 7 publications

References 197 publications

A High-Homology Region in Bacterial β-Barrel Pore-Forming Toxins

A High-Homology Region in Bacterial β-Barrel Pore-Forming Toxins

Perfringolysin O pore-forming complexes are predominantly integral multiples of six subunits

A High-Homology Region Provides the Possibility of Detecting β-Barrel Pore-Forming Toxins from Various Bacterial Species

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