Cholesterol-dependent cytolysin
| Cholesterol-binding cytolysin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Thiol_cytolysin | ||||||||
| Pfam | PF01289 | ||||||||
| InterPro | IPR001869 | ||||||||
| PROSITE | PDOC00436 | ||||||||
| OPM superfamily | 116 | ||||||||
| OPM protein | 1pfo | ||||||||
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| Available protein structures: | |
|---|---|
| Pfam | structures |
| PDB | RCSB PDB; PDBe; PDBj |
| PDBsum | structure summary |
The Thiol-activated Cholesterol-dependent Cytolysin (CDC) family (TC# 1.C.12) is a member of the MACPF superfamily. Cholesterol dependent cytolysins are a family of β-barrel pore-forming exotoxins that are secreted by gram-positive bacteria. CDCs are secreted as water-soluble monomers of 50-70 kDa, that when bound to the target cell, form a circular homo-oligomeric complex containing as many as 40 (or more) monomers. Through multiple conformational changes, the β-barrel transmembrane structure (~250 Å in diameter depending on the toxin) is formed and inserted into the target cell membrane. The presence of cholesterol in the target membrane is required for pore formation, though the presence of cholesterol is not required by all CDCs for binding. For example, Intermedilysin (ILY; TC# 1.C.12.1.5) secreted by will bind only to target membranes containing a specific protein receptor, independent of the presence of cholesterol, but cholesterol is required by intermedilysin (ILY; TC# 1.C.12.1.5) for pore formation. While the lipid environment of cholesterol in the membrane can affect toxin binding, the exact molecular mechanism that cholesterol regulates the cytolytic activity of the CDC is not fully understood.
Once the pore is formed within the target cell membrane, the regulation of the intracellular environment and what enters and leaves the cell is lost. The pore being ~250 Å in diameter is large enough to allow the loss of amino acids, nucleotides, small and large proteins, as well as ions (Ca2+,Na+, K+, etc.). The loss of calcium in particular, which is involved in multiple molecular pathways, will have a large impact on cell survival. The pore will also lead to an influx of water, which may lead to blebbing and cell death.
Bacteria invest energy into creating these toxins because they act as virulence factors. By targeting immune cells such as macrophages the bacteria will be protected against phagocytosis and destruction by respiratory burst.
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