TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*1.C.12.1.1









Perfringolysin O, PFO.  Phosphatidylcholine in the outer leaflet increases the cholesterol concentration required to induce PFO binding while phosphatidylethanolamine and phosphatidylserine in the inner leaflet of asymmetric vesicles stabilized the formation of a deeply inserted conformation that does not form pores, even though it contains transmembrane segments (Lin and London 2014). This conformation may represent an important intermediate stage in PFO pore formation.  Cholesterol recognition, oligomerization, and the conformational changes involved in pore formation have been reviewed (Johnson and Heuck 2014), and the involvement of the D1 domain in structural transitions leading to pore formation has been studied (Kacprzyk-Stokowiec et al. 2014). Interaction of PFO with cholesterol is sufficient to initiate an irreversible sequence of coupled conformational changes that extend throughout the toxin molecule and induce pore formation (Heuck et al. 2007).  Once this transmembrane beta-barrel protein is inserted, PFO assembles into pore-forming oligomers containing 30-50 PFO monomers. These form a pore of up to 300 Å, far exceeding the size of most other proteinaceous pores.  Decreasing the length of the β-strands causes the pore to shrink (Lin et al. 2015).

Bacteria
Firmicutes
Perfringolysin O of Clostridium perfringens (P0C2E9)
*1.C.12.1.2









Alveolysin
Bacteria
Firmicutes
Alveolysin of Bacillus alvei (P23564)
*1.C.12.1.3









Cereolysin O (hemolysin I) (Ramarao and Sanchis 2013).

Bacteria
Firmicutes
Hemolysin I of Bacillus cereus (Q93LA9)
*1.C.12.1.4









Streptolysin O (transports NAD-glycohydrolase into the host cell) (Meehl and Caparon, 2004).  Injections into cells modulates cell metabolism which induces streptolysin synthesis and S. pyogenes growth (Baruch et al. 2014).

Bacteria
Firmicutes
Streptolysin O of Streptococcus pyogenes (P0C0I3)
*1.C.12.1.5









Pneumolysin (PLS) or Intermedilysin (ILY), the shortest members of the CDC family (Gonzalez et al., 2008). Exhibits a broad range of conductances (El-Rachkidy et al., 2008) and localizes to the cell wall of S. pneumoniae (Price and Camilli, 2009). Binding of ILY to human CD59 initiates a series of conformational changes within the toxin that result in the conversion of the soluble monomer into an oligomeric membrane-embedded pore complex. The assembly intermediates increase the sensitivity of the host cell to lysis by its complement membrane attack complex, apparently by blocking the hCD59-binding site for complement proteins C8α and C9 (LaChapelle et al., 2009).  The herbal bioflavonoid, Apigenin, inhibits oligomerization of PLY and protects against pneumonia (Song et al. 2016).  Pneumolysin alters lysosomal integrity in epithelial cells, but not in macrophages, inducing lysosomal membrane permeabilization and release of lysosomal content (Malet et al. 2016). A four-step mechanism of membrane attachment and pore formation has been proosed (van Pee et al. 2016). Pneumolysin is both necessary and sufficient to promote inflammation, increasing shedding and causing transmission to others (Zafar et al. 2017).

Bacteria
Firmicutes
Pneumolysin of Streptococcus pneumoniae (P0C2J9)
*1.C.12.1.6









Ivanolysin
Bacteria
Firmicutes
Ivanolysin of Listeria ivanovii (P31831)
*1.C.12.1.7









Listeriolysin O, LLO (Viala et al., 2008). CFTR transiently increases phagosomal chloride concentrations after infection, potentiating pore formation and vacuole lysis. Thus, Listeria exploits mechanisms of cellular ion homeostasis to escape the phagosome (Radtke et al., 2011).  LLO is an example of a large beta-barrel pore that exhibits plasticity, controlled by environmental cues like pH (Podobnik et al. 2015).  Pore formation is a multistep process involving the sequential formation of arcs, slits, small rings and larger rings before formation of transmembrane pores (Mulvihill et al. 2015).  LLO promotes nanoscale membrane reorganization (Sarangi et al. 2016). It alters lysosomal integrity in epithelial cells, but not in macrophages, inducing lysosomal membrane permeabilization and release of lysosomal content (Malet et al. 2016).

Bacteria
Firmicutes
Listeriolysin O of Listeria monocytogenes (P13128)
*1.C.12.1.8









Suilysin (SLY, a hemolysin) of 497 aas is a pore-forming cholesterol-dependent cytolysin of S. suis and a true virulence factor (Tenenbaum et al. 2016). It plays a role during the development of S. suis meningitis in pigs and humans, and is a potential vaccine candidate.

Bacteria
Firmicutes
Hemolysin of Streptococcus suis (O85102)
*1.C.12.1.9









Pyolysin
Bacteria
Actinobacteria
Pyolysin of Arcanobacterium pyogenes (O31241)
*1.C.12.1.10









CDC family protein of 588 aas

Bacteria
Spirochaetes
CDC protein of Treponema medium
*1.C.12.1.11









CDC homologue of 511 aas

Bacteria
Deinococcus-Thermus
CDC protein of Deinococcus deserti
*1.C.12.1.12









Uncharacterized protein of 656 aas

Bacteria
Actinobacteria
UP of Streptomyces mobaraensis
*1.C.12.1.13









Intermedilysin of 532 aas and 1 N-terminal TMS.  It binds to membranes containing the human protein CD59 but forms pores only if the membrane contains sufficient cholesterol (Heuck et al. 2007).  CD59 is required for the specific coordination of intermedilysin (ILY) monomers and for triggering collapse of an oligomeric prepore. Movement of Domain 2 with respect to Domain 3 of ILY is essential for forming a late prepore intermediate that releases CD59, while the role of cholesterol may be limited to insertion of the TMSs (Boyd et al. 2016).

Bacteria
Firmicutes
Intermedilysin of Streptococcus intermedius
*1.C.12.2.1









Flavomodulin
Bacteria
Bacteroidetes/Chlorobi group
Flavomodulin of Flavobacterium psychrophilum (A6GVU3)
*1.C.12.2.2









Uncharacterized protein of 373 aas

Bacteria
Bacteroidetes/Chlorobi group
UP of Prevotella micans
*1.C.12.2.3









Tetanolysin O of 369 aas.  A three dimensional model of the toxin is availalbe (Skariyachan et al. 2012).

Bacteria
Bacteroidetes/Chlorobi group
Tetanolysin O of Capnocytophaga canimorsus
*1.C.12.2.4









CDC homologue of 489 aas

Bacteria
Bacteroidetes/Chlorobi group
CDC homologue of Chryseobacterium indologenes
*1.C.12.3.1









Hypothetical Protein, HP
Bacteria
Cyanobacteria
HP of Nostoc sp. PCC7120 (Q8YX86)
*1.C.12.3.2









Cytolysin, a secreted calcineurin-like phosphatase of 361 aas

Bacteria
Proteobacteria
Cytolysin of Mesorhizobium loti
*1.C.12.3.3









Cytolysin, a secreted calcineurin-like phosphatase of458 aas

Bacteria
Proteobacteria
Cytolysin of Candidatus Liberibacter americanus