TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*1.C.3.1.1









α-Hemolysin (alpha haemolysin; Hly; Hla; α-toxin). Fragments (13-293 aas) form heptamers like the native full length protein, but a fragment with aas 72-293 formed heptamers, octamers and nonamers. All formed Cl- permeable β-barrel channels (Vécsey-Semjén et al., 2010). The 3-d structure is available (PDB#7AHL). Both symmetry and size of cyclodextrin inhibitors and the toxin pore are important for effective inhibition (Yannakopoulou et al., 2011).  Oxoxylin A inhibits hemolysis by hindering self assembly of the hepatmeric pore in which two β-strands are contributed by each subunit (Song et al. 1996; Dong et al. 2013).  Applications of pore-forming α-haemolysin include small- and macromolecule-sensing, targeted cancer therapy, and drug delivery (Gurnev and Nestorovich 2014). Sugawara et al. 2015 studied pore formation. Structural comparisons among monomer, prepore and pore revealed a series of motions in which the N-terminal amino latch released upon oligomerization destroys its own key hydrogen bond betweem Asp45 and Try118. This action initiates the protrusion of the prestem. A Y118F mutant and the N-terminal truncated mutant markedly decreased the hemolytic activity, indicating the importance of the key hydrogen bond and the N-terminal amino latch for pore formation. A dynamic molecular mechanism of pore formation was proposed (Sugawara et al. 2015). Release of ATP from cells may occur directly through transmembrane pores formed by α-toxin (Baaske et al. 2016). The amino latch of staphylococcal alpha-hemolysin functions in pore formation via an co-operative interaction between the N terminus and position 217 (Jayasinghe et al. 2006).

PLEKHA7 and other junctional proteins are host factors mediating death by S. aureus alpha-toxin. ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C-terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11. ADAM10 is locked at junctions through binding of its cytoplasmic C terminus to afadin. Junctionally clustered ADAM10 supports the efficient formation of stable toxin pores. Disruption of the PLEKHA7-PDZD11 complex inhibits ADAM10 and toxin junctional clustering. This promotes toxin pore removal from the cell surface through an actin- and macropinocytosis-dependent process, resulting in cell recovery from initial injury and survival. Thus, a dock-and-lock molecular mechanism targets ADAM10 to junctions, providing a paradigm for how junctions may regulate transmembrane receptors through their clustering (Shah et al. 2018).

Bacteria
Firmicutes
α-hemolysin of Staphylococcus aureus
*1.C.3.2.1









Hemolysin II

Bacteria
Firmicutes
Hemolysin II of Bacillus cereus
*1.C.3.2.2









β-toxin

Bacteria
Firmicutes
β-toxin of Clostridium perfringens
*1.C.3.2.3









Cytotoxin
Bacteria
Firmicutes
Cytotoxin CytK of Bacillus cereus
*1.C.3.2.4









Necrotic enteritis toxin B precursor, NetB (Keyburn et al., 2008)

Bacteria
Firmicutes
NetB of Clostridium perfringens (A8ULG6)
*1.C.3.2.5









CctA (Clostridium chauvoei toxin A; 317 aas) is the main cytotoxic and haemolytic substance secreted by C. chauvoei.  Vaccination of guinea pigs with CctA in the form of a fusion protein with the E. coli heat labile toxin B subunit (rCctA::LTB) as a peptide adjuvant protected the animals against challenge with spores of virulent C. chauvoei., (Frey et al. 2012).

Bacteria
Firmicutes
Cytotoxin of Clostridium chauvoei

 
*1.C.3.2.6









Necrotizing enteritis toxin, NetF, of 305 aas.  NetF-producing type A Clostridium perfringens is an important cause of canine and foal necrotizing enteritis. NetF, related to the β-sheet pore-forming Leukocidin/Hemolysin superfamily, is considered a major virulence factor for this disease. The NetF receptor is probably a sialic acid-containing glycoprotein (Mehdizadeh Gohari et al. 2018).

Bacteria
Firmicutes
NetF of Clostridium perfringens
*1.C.3.3.1









Leucocidin/Hemolysin family member, LHF
Bacteria
Proteobacteria
LHF member of Vibrio species Ex25, (EDN58324)
*1.C.3.3.2









Leucocidin/Hemolysin toxin family member.  90% identical to a Leukocidin of Vibrio proteolyticus of 305 aas that plays an important role in virulence (Ray et al. 2016).

Bacteria
Proteobacteria
V12G01_16082 of Vibrio alginolyticus (Q1V718)
*1.C.3.4.1









Leucocidin chain F.  3-D structures of the prepore reveal that this is substantially different from the pore structure.  The structures revealed a disordered bottom half of the beta-barrel corresponding to the transmembrane region, and a rigid upper extramembrane half (Yamashita et al. 2014). LukF can form an octameric pore with 4 subunits of LukF and 4 subunits of LukS (TC# 1.C.3.4.3) (Jayasinghe and Bayley 2005).  Panton-Valentine leukocidin (PVL, encoded by lukSF-PV genes) is a bi-component and pore-forming toxin carried by different staphylococcal bacteriophages (Zhao et al. 2016).

Bacteria
Firmicutes
Leucocidin chain F (LukF) of Staphylococcus aureus (Q53747)
*1.C.3.4.2









Two component β-barrel γ-haemolysin, HlgA·HlgB. Tomita et al. (2011) reported that Hlg2 and LukF form a complex, and that Hlg pores form clusters that release hemoglobin from erythrocytes. The crystal structure of this octameric pore (PDB# 3B07; 2QK7) reveals the beta-barrel pore formation mechanism by the two components (Yamashita et al., 2011).  Dominant-negative mutant toxins may provide novel therapeutics to combat S. aureus infection (Reyes-Robles et al. 2016).  S. aureus beta-barrel pore-forming cytotoxins, including the identification of the toxin receptors on host cells, and their roles in pathogenesis have been reviewed (Reyes-Robles and Torres 2016).

Bacteria
Firmicutes
HlgA·HlgB of Staphylococcus aureus
*1.C.3.4.3









Two component β-barrel γ-haemolysin, HlgC·HlgB. HglC is identical to Leucocidin chain S (LukS) (P31716), and HlgB is identical to the HlgB protein listed under TC# 1.C.3.4.2 (Roblin et al. 2008). The pore-forming regions are initially folded up on the surfaces of the soluble precursors. To create the transmembrane pores, these regions must extend and refold into membrane-inserted beta-barrels (Tilley and Saibil 2006).

Bacteria
Firmicutes
HlgC·HlgB of Staphylococcus aureus
*1.C.3.4.4









Equid-adapted leukocidin PQ, LukPQ, of 311 (LukP) and 326 aas (LukQ), respectively (Koop et al. 2017).

Bacteria
Firmicutes
LukPQ of Staphylococcus aureus
*1.C.3.4.5









Beta-channel-forming cytolysin, the  synergohymenotropic toxin, of 310 aas.  Bacterial infections from Staphylococcus pseudintermedius are the most common cause of skin infections (pyoderma) affecting dogs. Two component pore-forming leukocidins are a family of potent toxins secreted by staphylococci and consist of S (slow) and F (fast) components. They impair the innate immune system, the first line of defense against these pathogens. Seven different leukocidins have been characterized in Staphylococcus aureus, some of which are host and cell specific. Abouelkhair et al. 2018 identified two proteins, named "LukS-I" and "LukF-I", encoded on a degenerate prophage contained in the genome of S. pseudintermedius isolates. The killing effect of recombinant S. pseudintermedius LukS-I together with LukF-I on canine polymorphonuclear leukocytes depended on both constituents of the two-component pore-forming leukocidin.

Bacteria
Firmicutes
LukS-I/LukF-I of Staphylococcus pseudintermedius