Branching out the aerolysin, ETX/MTX-2 and Toxin_10 family of pore forming proteins

2021 ◽  
pp. 107570
Author(s):  
Chris J. Lacomel ◽  
Michelle A. Dunstone ◽  
Bradley A. Spicer
Keyword(s):  
Pore Forming Proteins

Sticholysins, pore-forming proteins from a marine anemone can induce maturation of dendritic cells through a TLR4 dependent-pathway

2021 ◽  
Author(s):  
Rady J. Laborde ◽  
Mayari E. Ishimura ◽  
Lianne Abreu-Butin ◽  
Catarina V. Nogueira ◽  
Daniel Grubaugh ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Pore Forming Proteins ◽  
Dependent Pathway

Natural Pore Forming Proteins: Paneth Cell Cryptdins

2000 ◽  
pp. 149-156
Author(s):  
W. I. Lencer ◽  
D. Merlin ◽  
A. J. Ouellette ◽  
M. E. Selsted ◽  
J. L. Madara
Keyword(s):  
Paneth Cell ◽  
Pore Forming Proteins

scholarly journals A Deadly Cargo: Gene Repertoire of Cytotoxic Effector Proteins in the Camelidae

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 304
Author(s):  
Ján Futas ◽  
Jan Oppelt ◽  
Pamela Anna Burger ◽  
Petr Horin
Keyword(s):  
Cytotoxic T Cells ◽  
Effector Proteins ◽  
Target Cells ◽  
Gene Repertoire ◽  
Interspecific Differences ◽  
Genes Encoding ◽  
Bactrian Camels ◽  
Pore Forming Proteins ◽  
Sequence Similarities ◽  
Cytotoxic Effector

Cytotoxic T cells and natural killer cells can kill target cells based on their expression and release of perforin, granulysin, and granzymes. Genes encoding these molecules have been only poorly annotated in camelids. Based on bioinformatic analyses of genomic resources, sequences corresponding to perforin, granulysin, and granzymes were identified in genomes of camelids and related ungulate species, and annotation of the corresponding genes was performed. A phylogenetic tree was constructed to study evolutionary relationships between the species analyzed. Re-sequencing of all genes in a panel of 10 dromedaries and 10 domestic Bactrian camels allowed analyzing their individual genetic polymorphisms. The data showed that all extant Old World camelids possess functional genes for two pore-forming proteins (PRF1, GNLY) and six granzymes (GZMA, GZMB, GZMH, GZMK, GZMM, and GZMO). All these genes were represented as single copies in the genome except the GZMH gene exhibiting interspecific differences in the number of loci. High protein sequence similarities with other camelid and ungulate species were observed for GZMK and GZMM. The protein variability in dromedaries and Bactrian camels was rather low, except for GNLY and chymotrypsin-like granzymes (GZMB, GZMH).

scholarly journals P-glycoprotein Does Not Protect Cells against Cytolysis Induced by Pore-forming Proteins

2001 ◽  
Vol 276 (20) ◽  
pp. 16667-16673 ◽  
Author(s):  
Ricky W. Johnstone ◽  
Kellie M. Tainton ◽  
Astrid A. Ruefli ◽  
Christopher J. Froelich ◽  
Loretta Cerruti ◽  
...  
Keyword(s):  
P Glycoprotein ◽  
Pore Forming Proteins

Genetically-Engineered Protease-Activated Triggers in a Pore-Forming Protein

1993 ◽  
Vol 330 ◽  
Author(s):  
Barbara Walker ◽  
Nathan Walsh ◽  
Hagan Bayley
Keyword(s):  
Genetic Engineering ◽  
Cancer Cells ◽  
Pore Formation ◽  
Polypeptide Chain ◽  
Genetically Engineered ◽  
Recognition Sequence ◽  
Selective Activation ◽  
Selective Destruction ◽  
Pore Forming Proteins ◽  
Central Loop

ABSTRACTProtease-activated triggers have been introduced Into a pore-forming protein, staphylococcal a-hemolysin (αHL). The hemolysin was remodeled by genetic engineering to form two-chain constructs with redundant polypeptide sequences at the central loop, the Integrity of which Is crucial for efficient pore formation. The new hemolysins are activated when the polypeptide extensions are removed by proteases. By alterating the protease recognition sequence in the loop, selective activation by specified proteases can be obtained. Protease-triggered pore-forming proteins might be used for the selective destruction of cancer cells that bear tumor-associated proteases. When certain two-chain constructs are treated with proteases, a full-length polypeptide chain forms as the result of a protease-mediated transpeptidation reaction. This reaction might be used to produce chimeric hemolysins that are Inaccessible by conventional routes.

Cytolytic Pore-Forming Proteins

1988 ◽  
pp. 9-43
Author(s):  
John Ding-E Young ◽  
Chau-Ching Liu ◽  
Lauren G. Leong ◽  
Angela Damiano ◽  
Marie A. Dinome ◽  
...  
Keyword(s):  
Pore Forming Proteins

scholarly journals A Profound Membrane Reorganization Defines Susceptibility of Plasmodium falciparum Infected Red Blood Cells to Lysis by Granulysin and Perforin

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria Andrea Hernández-Castañeda ◽  
Marilyne Lavergne ◽  
Pierina Casanova ◽  
Bryan Nydegger ◽  
Carla Merten ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Molecular Mechanisms ◽  
Γδ T Cells ◽  
Parasite Growth ◽  
Complex Life Cycle ◽  
Cholesterol Depletion ◽  
Host Cell Membrane ◽  
Pore Forming Proteins

Malaria remains one of the most serious health problems in developing countries. The causative agent of malaria, Plasmodium spp., have a complex life cycle involving multiple developmental stages as well as different morphological, biochemical and metabolic requirements. We recently found that γδ T cells control parasite growth using pore-forming proteins to deliver their cytotoxic proteases, the granzymes, into blood residing parasites. Here, we follow up on the molecular mechanisms of parasite growth inhibition by human pore-forming proteins. We confirm that Plasmodium falciparum infection efficiently depletes the red blood cells of cholesterol, which renders the parasite surrounding membranes susceptible to lysis by prokaryotic membrane disrupting proteins, such as lymphocytic granulysin or the human cathelicidin LL-37. Interestingly, not the cholesterol depletion but rather the simultaneous exposure of phosphatidylserine, a negatively charged phospholipid, triggers resistance of late stage parasitized red blood cells towards the eukaryotic pore forming protein perforin. Overall, by revealing the molecular events we establish here a pathogen-host interaction that involves host cell membrane remodeling that defines the susceptibility towards cytolytic molecules.

scholarly journals Activity of the Pore-Forming Virulence Factor Listeriolysin O Is Reversibly Inhibited by Naturally Occurring S-Glutathionylation

2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Jonathan L. Portman ◽  
Qiongying Huang ◽  
Michelle L. Reniere ◽  
Anthony T. Iavarone ◽  
Daniel A. Portnoy
Keyword(s):  
Protein Function ◽  
Inhibitory Effect ◽  
Cysteine Residue ◽  
Infection Model ◽  
Listeriolysin O ◽  
Content Type ◽  
Pore Forming Proteins

ABSTRACT Cholesterol-dependent cytolysins (CDCs) represent a family of homologous pore-forming proteins secreted by many Gram-positive bacterial pathogens. CDCs mediate membrane binding partly through a conserved C-terminal undecapeptide, which contains a single cysteine residue. While mutational changes to other residues in the undecapeptide typically have severe effects, mutation of the cysteine residue to alanine has minor effects on overall protein function. Thus, the role of this highly conserved reactive cysteine residue remains largely unknown. We report here that the CDC listeriolysin O (LLO), secreted by the facultative intracellular pathogen Listeria monocytogenes, was posttranslationally modified by S-glutathionylation at this conserved cysteine residue and that either endogenously synthesized or exogenously added glutathione was sufficient to form this modification. When recapitulated with purified protein in vitro, this modification completely ablated the activity of LLO, and this inhibitory effect was fully reversible by treatment with reducing agents. A cysteine-to-alanine mutation in LLO rendered the protein completely resistant to inactivation by S-glutathionylation, and a mutant expressing this mutation retained full hemolytic activity. A mutant strain of L. monocytogenes expressing the cysteine-to-alanine variant of LLO was able to infect and replicate within bone marrow-derived macrophages indistinguishably from the wild type in vitro, yet it was attenuated 4- to 6-fold in a competitive murine infection model in vivo. This study suggests that S-glutathionylation may represent a mechanism by which CDC-family proteins are posttranslationally modified and regulated and help explain an evolutionary pressure to retain the highly conserved undecapeptide cysteine.

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