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1.C.43 The Earthworm Lysenin Toxin (Lysenin) Family

Lysenin (also called eiseniapore) is a 297 aa protein that specifically binds to sphingomyelin and cholesterol-containing membranes of mammalian cells, including red blood cells and tissue cells, and induces lysis. It is derived from the coelomic fluid of the earthworm, Eisenia foetida. The protein binds to both sphingomyelin and galactosyl ceramide but not to ceramide or galactosyl sphingosine. It probably causes lysis by producing oligomeric protein pores in the target membrane. Lysenin has been reported to have antibacterial activity. It shows weak motif similarity to crystal protein, CryET33.the crystal structure of the lysenin pore and provide insights into its assembly mechanism. The lysenin pore is assembled from nine monomers via dramatic reorganization of almost half of the monomeric subunit structure leading to a β-barrel pore ∼10 nm long and 1.6-2.5 nm wide. The lysenin pore is devoid of additional luminal compartments as commonly found in other toxin pores. Mutagenic analysis and atomic force microscopy imaging, together with these structural insights, suggest a mechanism for pore assembly for lysenin. These insights are relevant to the understanding of pore formation by other aerolysin-like pore-forming toxins, which often represent crucial virulence factors in bacteria.

Lysenin forms stable oligomers upon membrane binding and causes cell lysis. To get insight into the mechanism of the transition of lysenin from a soluble to a membrane-bound form, the binding of lysenin to lipid membranes were studied by Hereć et al. (2008). The total content of alpha-helices, turns and loops, and beta-structures did not change when it became membrane bound. The alpha-helical component was oriented at 41 degrees to the normal to the membrane, indicating that this protein segment could be anchored in the hydrophobic core of the membrane (Hereć et al., 2008).

The crystal structure of the lysenin pore has been reported (Podobnik et al. 2016). The pore is assembled from nine monomers via dramatic reorganization of almost half of the monomeric subunit structure leading to a β-barrel pore ∼10 nm long and 1.6-2.5 nm wide. Mutagenic analysis and atomic force microscopy imaging suggested a mechanism for pore assembly for lysenin (Podobnik et al. 2016).

The generalized reaction catalyzed by members of the Lysenin family is:

ions (in) ions (out).


This family belongs to the: Aerolysin Superfamily.

References associated with 1.C.43 family:

Bryant, S., N. Shrestha, P. Carnig, S. Kosydar, P. Belzeski, C. Hanna, and D. Fologea. (2016). Purinergic control of lysenin''s transport and voltage-gating properties. Purinergic Signal 12: 549-559. 27318938
Hereć, M., M. Gagoś, M. Kulma, K. Kwiatkowska, A. Sobota, and W.I. Gruszecki. (2008). Secondary structure and orientation of the pore-forming toxin lysenin in a sphingomyelin-containing membrane. Biochim. Biophys. Acta. 1778: 872-879. 18178147
Kwiatkowska, K., R. Hordejuk, P. Szymczyk, M. Kulma, A.B. Abdel-Shakor, A. Płucienniczak, K. Dołowy, A. Szewczyk, and A. Sobota. (2007) Lysenin-His, a sphingomyelin-recognizing toxin, requires tryptophan 20 for cation-selective channel assembly but not for membrane binding. Mol. Membr. Biol. 24: 121-134. 17453419
Podobnik, M., P. Savory, N. Rojko, M. Kisovec, N. Wood, R. Hambley, J. Pugh, E.J. Wallace, L. McNeill, M. Bruce, I. Liko, T.M. Allison, S. Mehmood, N. Yilmaz, T. Kobayashi, R.J. Gilbert, C.V. Robinson, L. Jayasinghe, and G. Anderluh. (2016). Crystal structure of an invertebrate cytolysin pore reveals unique properties and mechanism of assembly. Nat Commun 7: 11598. 27176125
Sekizawa, Y., T. Kubo, H. Kobayashi, T. Nakajima, and S. Natori. (1997). Molecular cloning of cDNA for lysenin, a novel protein in the earthworm Eisenia foetida that causes contraction of rat vascular smooth muscle. Gene. 191: 97-102. 9210594
Shogomori, H. and T. Kobayashi. (2008). Lysenin: a sphingomyelin specific pore-forming toxin. Biochim. Biophys. Acta. 1780(3): 612-618. 17980968
Yamaji, A., Y. Sekizawa, K. Emoto, H. Sakuraba, K. Inoue, H. Kobayashi and M. Umeda (1998). Lysenin, a novel sphingomyelin-specific binding protein. J. Biol. Chem. 273: 5300-5306. 9478988