1.C.4.8.1
Cellular endolysosome-modulating aerolysin-like pore-forming protein, ALP1, of 156 aas (Wang et al. 2020). The protein shows sequence similarity in its N-terminal half with family 1.C.73 members and in its C-terminal half with family 1.C.4 members. βγ-CAT is a complex of an ALP (BmALP1) and a trefoil factor (BmTFF3) in the firebelly toad (Bombina maxima). It is a secreted endogenous pore-forming protein that modulates the biochemical properties of endolysosomes by inducing pore formation. BmALP3, a paralog of BmALP1 that lacks membrane pore-forming capacity, like BmALP1, has a conserved cysteine in its C-terminal regions. BmALP3 is readily oxidized to a disulfide bond-linked homodimer, and this homodimer can oxidize BmALP1 via disulfide bond exchange, resulting in the dissociation of βγ-CAT subunits and elimination of its biological activity. BmALP3 senses environmental oxygen tension in vivo, leading to modulation of βγ-CAT activity. This C-terminal cysteine site is well conserved in numerous vertebrate ALPs, suggesting that it is a regulatory ALP (BmALP3) that modulates the activity on the active ALP (BmALP1) in a redox-dependent manner (Wang et al. 2020). An aerolysin-like pore-forming protein complex targets viral envelope to inactivate herpes simplex virus type 1 (Liu et al. 2021).