Lysenin

Lysenin is a pore-forming toxin (PFT) present in the coelomic fluid of the earthworm Eisenia fetida.

After a conformational change, which could be triggered by a decrease of pH, the oligomer is inserted into the membrane in the so-called pore state.

Using X-ray crystallography, lysenin was classified as a member of the Aerolysin protein family by structure and function.

[7] Cholesterol, which enhances oligomerization, provides a stable platform with high lateral mobility where monomer-monomer encounters are more probable.

[11] This difference in height between the detergent belt and the sphingomyelin/cholesterol bilayer implies a bend of the membrane in the region surrounding the pore, called negative mismatch.

[14] When lysenin monomers bind to sphingomyelin-enriched membrane regions, they provide a stable platform with a high lateral mobility, hence favouring the oligomerization.

[20] However, complete oligomerization into the nonamer is not a requisite for the insertion, since incomplete oligomers in the pore state can be found.

It has been suggested that lysenin may play a role as a defence mechanism against attackers such as bacteria, fungi or small invertebrates.

[28] However, lysenin's activity is dependent upon binding to sphingomyelin, which is not present in the membranes of bacteria, fungi or most invertebrates.

[29] Another hypothesis is that the earthworm, which is able to expel coelomic fluid under stress,[30][31] generates an avoidance behaviour to its vertebrate predators (such as birds, hedgehogs or moles).

[32] If that is the case, the expelled lysenin might be more effective if the coelomic fluid reaches the eye, where the concentration of sphingomyelin is ten times higher than in other body organs.

[33] A complementary hypothesis is that the pungent smell of the coelomic fluid - giving the earthworm its specific epithet foetida - is an anti-predator adaptation.

[36] There have also been over three decades of studies into finding suitable pores for converting into nanopore sequencing systems that can have their conductive properties tuned by point mutation.

Lysenin water-soluble monomeric X-ray structure ( PDB : 3ZXD ​). Receptor binding domain on right in grey. Pore Forming Module (PFM) on left with region previously thought to be responsible for β-barrel formation in green. Additional region now known to be important in β-barrel formation in yellow (from X-ray data),
Lysenin mechanism of action Scheme. a) Lysenin monomers are segregated as soluble proteins that bind specifically to sphingomyelin by its receptor binding domain. After binding, and reach a certain density, the oligomerization starts. b) After a complete oligomerization, the prepore is formed. The prepore model shown here was assembled from the monomer structure and aligned with the pore structure ( PDB : 5GAQ ​) by their receptor-binding domains (residues 160 to 297). The height of the prepore was set to agree with the Atomic Force Microscopy measurements. c) Membrane inserted Lysenin assembly ( PDB : 5GAQ ​). The height of the pore was measured from the detergent belt to the last residue, assuming that the detergent belt corresponds with the part of the pore surrounded by the membrane. The membrane was placed in the β-barrel of the pore to match with the detergent belt, that englobe all the hydrophobic residues of the β-barrel. The hydrophobic surface colour scale is according to the hydrophobicity scale of Kyte and Doolittle.