1.C.43.1.1
Lysenin of 297 aas and 1 N-terminal TMS, a sphingomyelin-specific pore-forming toxin from earthworms; causes contraction of rat vascular smooth muscle. (Sekizawa et al., 1997; Shogomori and Kobayashi, 2007). Trp-20 is required for cation selective channel assembly (Kwiatkowska et al., 2007).  Adenosine phosphates control the activity of lysenin channels inserted into planar lipid membranes with respect to their macroscopic conductance and voltage-induced gating. Addition of ATP, ADP, or AMP decreased the macroscopic conductance of lysenin channels in a concentration-dependent manner, with ATP being the most potent inhibitor and AMP the least (Bryant et al. 2016). lysenin can specifically interact with sphingomyelin, and may confer innate immunity against parasites by attacking the membranes of the parasites to form pores (Pang et al. 2019).  Upon binding to sphingomyelin (SM)-containing membranes, lysenin undergoes a series of structural changes promoting the conversion of water-soluble monomers into oligomers, leading to its insertion into the membrane and the 2-step formation of a lytic beta-barrel pore (Kulma et al. 2019). Structural stabilization of the lysenin prepore starts at the site of  initial interaction with the lipid membrane and is transmitted to the twisted beta-sheet of the N-terminal domain (Kulma et al. 2019). 3-d structures are available (PDB# 5EC5; 3ZXD; 3ZX7). The beta pore-forming toxins (beta-PFTs) are cytotoxic proteins produced as soluble monomers, which cluster and oligomerize at the membrane of the target host cells. Their initial oligomeric state, the prepore, is not cytotoxic. The beta-PFTs undergo a large structural transition to a second oligomeric state, the pore, which pierces the membrane of the host cell and is cytotoxic. Munguira et al. 2019 described the mechanism by which the rates of formation of the transmembrane pores correlate with the local levels of crowding for the beta-PFT lysenin.