Pathogenic Pore-Forming Proteins: Function and Host Response

Bischofberger, Mirko; Iacovache, Ioan; Goot, F. Gisou van der

doi:10.1016/j.chom.2012.08.005

Cited by 176 publications

(238 citation statements)

References 118 publications

(165 reference statements)

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“…VAP formation was observed upon PVAP overexpression in yeast, and in this case pyramids were observed in all intracellular membranes, including those of the Golgi apparatus, nucleus and mitochondria. In combination, these observations suggest that PVAP inserts into the membrane spontaneously and in a Sec-independent manner, similar to tail-anchored proteins and bacterial pore-forming toxins (Borgese and Fasana 2011;Bischofberger et al 2012). Consequently, PVAP has the ability to self-assemble into VAPs in virtually any lipid bilayer and thus remodel membranes with fundamentally different lipid chemistry (ester or ether based for bacteria/eukarya or archaea, respectively) under a range of temperatures and acidities (37-80°C, pH 3-7) (Albers and Meyer 2011;Quax et al 2011;Daum et al 2014).…”

Section: Protein Properties Of Pvapmentioning

confidence: 79%

Structure and assembly mechanism of virus-associated pyramids

Quax

Daum

2017

Biophys Rev

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Viruses have developed intricate molecular machines to infect, replicate within and escape from their host cells. Perhaps one of the most intriguing of these mechanisms is the pyramidal egress structure that has evolved in archaeal viruses, such as SIRV2 or STIV1. The structure and mechanism of these virus-associated pyramids (VAPs) has been studied by cryo-electron tomography and complementary biochemical techniques, revealing that VAPs are formed by multiple copies of a virus-encoded 10-kDa protein (PVAP) that integrate into the cell membrane and assemble into hollow, sevenfold symmetric pyramids. In this process, growing VAPs puncture the protective surface layer and ultimately open to release newly replicated viral particles into the surrounding medium. PVAP has the striking capability to spontaneously integrate and self-assemble into VAPs in biological membranes of the archaea, bacteria and eukaryotes. This renders the VAP a universal membrane remodelling system. In this review, we provide an overview of the VAP structure and assembly mechanism and discuss the possible use of VAPs in nanobiotechnology.

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Section: Protein Properties Of Pvapmentioning

confidence: 79%

Structure and assembly mechanism of virus-associated pyramids

Quax

Daum

2017

Biophys Rev

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“…For the purpose of invasion, several pathogenic bacteria produce PFTs, such as β-barrel-type aerolysins, which can oligomerize and form pores in host-cell membranes (12,13). The aerolysin domain is defined according to its structural similarity to the transmembrane domain of aerolysin toxins.…”

mentioning

confidence: 99%

Host-derived, pore-forming toxin–like protein and trefoil factor complex protects the host against microbial infection

Xiang

Yan

Guo

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

112

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Aerolysins are virulence factors belonging to the bacterial β-poreforming toxin superfamily. Surprisingly, numerous aerolysin-like proteins exist in vertebrates, but their biological functions are unknown. βγ-CAT, a complex of an aerolysin-like protein subunit (two βγ-crystallin domains followed by an aerolysin pore-forming domain) and two trefoil factor subunits, has been identified in frogs (Bombina maxima) skin secretions. Here, we report the rich expression of this protein, in the frog blood and immune-related tissues, and the induction of its presence in peritoneal lavage by bacterial challenge. This phenomena raises the possibility of its involvement in antimicrobial infection. When βγ-CAT was administrated in a peritoneal infection model, it greatly accelerated bacterial clearance and increased the survival rate of both frogs and mice. Meanwhile, accelerated Interleukin-1β release and enhanced local leukocyte recruitments were determined, which may partially explain the robust and effective antimicrobial responses observed. The release of interleukin-1β was potently triggered by βγ-CAT from the frog peritoneal cells and murine macrophages in vitro. βγ-CAT was rapidly endocytosed and translocated to lysosomes, where it formed high molecular mass SDS-stable oligomers (>170 kDa). Lysosomal destabilization and cathepsin B release were detected, which may explain the activation of caspase-1 inflammasome and subsequent interleukin-1β maturation and release. To our knowledge, these results provide the first functional evidence of the ability of a host-derived aerolysin-like protein to counter microbial infection by eliciting rapid and effective host innate immune responses. The findings will also largely help to elucidate the possible involvement and action mechanisms of aerolysin-like proteins and/or trefoil factors widely existing in vertebrates in the host defense against pathogens.innate immunity | infectious disease | interleukin-1beta

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“…PFT at sub-lytic concentrations and during the first hours of incubation with cells provoke a significant loss of intracellular K + due to membrane damage. However, in the following hours, intracellular K + level can increase as an indication of cell recovery (Bischofberger et al 2012). Strikingly, it has been found that membrane recovery upon StII damage takes place in a time scale similar to that upon LLO damage even though these two PFT form pores that differ greatly in size.…”

Section: Interaction With Nucleated Cellsmentioning

confidence: 97%

“…Despite the great diversity of PFT in terms of source, structure or physiological role, they all follow a similar mode of action (Bischofberger et al 2012;Ros and Garcia-Saez 2015). PFT are produced as soluble molecules and then become membrane-associated proteins forming water-filled pores in the membrane of the target cells that disrupt cell homeostasis through the increase of the non-selective passage of molecules.…”

Section: Cellular Mechanisms Triggered Upon Sts-membrane Interaction:mentioning

confidence: 99%

“…Secreted in soluble form, they undergo conformational changes upon different stimuli, allowing them to create a pore in the host membrane. These toxins exhibit a very broad taxonomic distribution from bacteria to mammals (Gonzalez et al 2008;Bischofberger et al 2012;Alves et al 2014), with bacterial PFT the best characterized to date (Peraro and van der Goot 2016). PFT can be classified into two broad groups: α-pore-forming proteins (PFP) and β-PFP, depending on the secondary structural elements involved in pore architecture (Parker and Feil 2005;Iacovache et al 2010).…”

Section: Introducing the Toxinsmentioning

confidence: 99%

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Biophysical and biochemical strategies to understand membrane binding and pore formation by sticholysins, pore-forming proteins from a sea anemone

et al. 2017

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Actinoporins constitute a unique class of poreforming toxins found in sea anemones that are able to bind and oligomerize in membranes, leading to cell swelling, impairment of ionic gradients and, eventually, to cell death. In this review we summarize the knowledge generated from the combination of biochemical and biophysical approaches to the study of sticholysins I and II (Sts, StI/II), two actinoporins largely characterized by the Center of Protein Studies at the University of Havana during the last 20 years. These approaches include strategies for understanding the toxin structure-function relationship, the protein-membrane association process leading to pore formation and the interaction of toxin with cells. The rational combination of experimental and theoretical tools have allowed unraveling, at least partially, of the complex mechanisms involved in toxin-membrane interaction and of the molecular pathways triggered upon this interaction. The study of actinoporins is important not only to gain an understanding of their biological roles in anemone venom but also to investigate basic molecular mechanisms of protein insertion into membranes, protein-lipid interactions and the modulation of protein conformation by lipid binding. A deeper knowledge of the basic molecular mechanisms involved in Sts-cell interaction, as described in this review, will support the current investigations conducted by our group which focus on the design of immunotoxins against tumor cells and antigen-releasing systems to cell cytosol as Stsbased vaccine platforms.

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Pathogenic Pore-Forming Proteins: Function and Host Response

Cited by 176 publications

References 118 publications

Structure and assembly mechanism of virus-associated pyramids

Structure and assembly mechanism of virus-associated pyramids

Host-derived, pore-forming toxin–like protein and trefoil factor complex protects the host against microbial infection

Biophysical and biochemical strategies to understand membrane binding and pore formation by sticholysins, pore-forming proteins from a sea anemone

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