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Biological effects of listeriolysin O: implications for vaccination.

Hernández-Flores KG, Vivanco-Cid H - Biomed Res Int (2015)

Bottom Line: The spectrum of biological activities induced by LLO includes cytotoxicity, apoptosis induction, endoplasmic reticulum stress response, modulation of gene expression, intracellular calcium oscillations, and proinflammatory activity.In addition, LLO is a highly immunogenic toxin and the major target for innate and adaptive immune responses in different animal models and humans.Recently, the crystal structure of LLO has been published in detail.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, 91700 Veracruz, VER, Mexico ; Doctorado en Ciencias Biomédicas, Centro de Investigaciones Biomédicas, Universidad Veracruzana, 91000 Xalapa,VER, Mexico.

ABSTRACT
Listeriolysin O (LLO) is a thiol-activated cholesterol-dependent pore-forming toxin and the major virulence factor of Listeria monocytogenes (LM). Extensive research in recent years has revealed that LLO exerts a wide array of biological activities, during the infection by LM or by itself as recombinant antigen. The spectrum of biological activities induced by LLO includes cytotoxicity, apoptosis induction, endoplasmic reticulum stress response, modulation of gene expression, intracellular calcium oscillations, and proinflammatory activity. In addition, LLO is a highly immunogenic toxin and the major target for innate and adaptive immune responses in different animal models and humans. Recently, the crystal structure of LLO has been published in detail. Here, we review the structure-function relationship for this fascinating microbial molecule, highlighting the potential uses of LLO in the fields of biomedicine and biotechnology, particularly in vaccination.

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Related in: MedlinePlus

A structure-function relationship model of Listeriolysin O (LLO). LLO domains are represented in a different color: domain 1 blue, domain 2 yellow, domain 3 green, and domain 4 pink. Key residues or sequences for biological activity or immunogenicity are highlighted in red color. The LLO structure-function model was generated based on the crystal structure reported by Köster et al. [2] with PYMOL program.
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fig1: A structure-function relationship model of Listeriolysin O (LLO). LLO domains are represented in a different color: domain 1 blue, domain 2 yellow, domain 3 green, and domain 4 pink. Key residues or sequences for biological activity or immunogenicity are highlighted in red color. The LLO structure-function model was generated based on the crystal structure reported by Köster et al. [2] with PYMOL program.

Mentions: D3 is formed by a five-stranded antiparallel β-sheet, which is surrounded by six α-helices [2]. Previously, it has been described that three residues in the D3 region are important as a pH-sensor, comprising D208, E247, and D320 residues [8]. The recently published crystal structure shows that one Na+ and a water molecule are necessary to mediate the interactions of D208, E247, and Y206 from the central β-sheet with D320 and K316 from the second membrane-inserting helix bundle [2]. LLO conformation is regulated by temperature and pH-dependent mechanisms [8]. The pH sensor triggers the denaturation of LLO at neutral pH [8]. D4 is the most wide studied region in the LLO structure. D4 has eight β-sheets, which are organized forming a β-sandwich structure [2]. The major feature of the D4 is the presence of a highly conserved structural motif of 11 residues (ECTGLAWEWWR) in the C terminal region that is considered crucial for membrane binding and cytotoxic activity [1] (Figure 1).


Biological effects of listeriolysin O: implications for vaccination.

Hernández-Flores KG, Vivanco-Cid H - Biomed Res Int (2015)

A structure-function relationship model of Listeriolysin O (LLO). LLO domains are represented in a different color: domain 1 blue, domain 2 yellow, domain 3 green, and domain 4 pink. Key residues or sequences for biological activity or immunogenicity are highlighted in red color. The LLO structure-function model was generated based on the crystal structure reported by Köster et al. [2] with PYMOL program.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4385656&req=5

fig1: A structure-function relationship model of Listeriolysin O (LLO). LLO domains are represented in a different color: domain 1 blue, domain 2 yellow, domain 3 green, and domain 4 pink. Key residues or sequences for biological activity or immunogenicity are highlighted in red color. The LLO structure-function model was generated based on the crystal structure reported by Köster et al. [2] with PYMOL program.
Mentions: D3 is formed by a five-stranded antiparallel β-sheet, which is surrounded by six α-helices [2]. Previously, it has been described that three residues in the D3 region are important as a pH-sensor, comprising D208, E247, and D320 residues [8]. The recently published crystal structure shows that one Na+ and a water molecule are necessary to mediate the interactions of D208, E247, and Y206 from the central β-sheet with D320 and K316 from the second membrane-inserting helix bundle [2]. LLO conformation is regulated by temperature and pH-dependent mechanisms [8]. The pH sensor triggers the denaturation of LLO at neutral pH [8]. D4 is the most wide studied region in the LLO structure. D4 has eight β-sheets, which are organized forming a β-sandwich structure [2]. The major feature of the D4 is the presence of a highly conserved structural motif of 11 residues (ECTGLAWEWWR) in the C terminal region that is considered crucial for membrane binding and cytotoxic activity [1] (Figure 1).

Bottom Line: The spectrum of biological activities induced by LLO includes cytotoxicity, apoptosis induction, endoplasmic reticulum stress response, modulation of gene expression, intracellular calcium oscillations, and proinflammatory activity.In addition, LLO is a highly immunogenic toxin and the major target for innate and adaptive immune responses in different animal models and humans.Recently, the crystal structure of LLO has been published in detail.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, 91700 Veracruz, VER, Mexico ; Doctorado en Ciencias Biomédicas, Centro de Investigaciones Biomédicas, Universidad Veracruzana, 91000 Xalapa,VER, Mexico.

ABSTRACT
Listeriolysin O (LLO) is a thiol-activated cholesterol-dependent pore-forming toxin and the major virulence factor of Listeria monocytogenes (LM). Extensive research in recent years has revealed that LLO exerts a wide array of biological activities, during the infection by LM or by itself as recombinant antigen. The spectrum of biological activities induced by LLO includes cytotoxicity, apoptosis induction, endoplasmic reticulum stress response, modulation of gene expression, intracellular calcium oscillations, and proinflammatory activity. In addition, LLO is a highly immunogenic toxin and the major target for innate and adaptive immune responses in different animal models and humans. Recently, the crystal structure of LLO has been published in detail. Here, we review the structure-function relationship for this fascinating microbial molecule, highlighting the potential uses of LLO in the fields of biomedicine and biotechnology, particularly in vaccination.

Show MeSH
Related in: MedlinePlus